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midodrine

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Description

Midodrine is a synthetic α1-adrenergic agonist that is used to treat orthostatic hypotension. It works by constricting blood vessels, which increases blood pressure. Midodrine is typically taken orally. It is synthesized by reacting the amine 1-(2-aminoethyl)-2-imidazolidinone with 1-(2,6-dichlorophenyl)-4-methyl-1-pentanone. Midodrine is well-absorbed following oral administration and has a half-life of about 3 hours. The drug is metabolized by the liver and excreted in the urine. Midodrine is a potent vasoconstrictor that causes a rapid increase in blood pressure. It is also used to treat orthostatic hypotension associated with autonomic failure, multiple system atrophy, and Parkinson's disease. Midodrine has been shown to be effective in improving symptoms of orthostatic hypotension, such as dizziness, lightheadedness, and fainting. It is also being studied as a potential treatment for other conditions, such as urinary incontinence and premature ejaculation. Research on midodrine focuses on its potential for treating orthostatic hypotension and other conditions, as well as investigating its safety and efficacy in different populations.'

Midodrine: An ethanolamine derivative that is an adrenergic alpha-1 agonist. It is used as a vasoconstrictor agent in the treatment of HYPOTENSION. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

midodrine : An aromatic ether that is 1,4-dimethoxybenzene which is substituted at position 2 by a 2-(glycylamino)-1-hydroxyethyl group. A direct-acting sympathomimetic with selective alpha-adrenergic agonist activity, it is used (generally as its hydrochloride salt) as a peripheral vasoconstrictor in the treatment of certain hypotensive states. The main active moiety is its major metabolite, deglymidodrine. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID4195
CHEMBL ID1201212
CHEBI ID6933
SCHEMBL ID131436
SCHEMBL ID20996761
MeSH IDM0013860

Synonyms (97)

Synonym
(+-)-2-amino-n-(beta-hydroxy-2,5-dimethoxyphenethyl)acetamide
midodrina
CHEBI:6933 ,
rac-n-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]glycinamide
midodrinum
BRD-A79981887-003-05-7
DIVK1C_000955
KBIO1_000955
n-{2-[2,5-bis(methyloxy)phenyl]-2-hydroxyethyl}glycinamide
SPECTRUM_001641
BSPBIO_003150
NCGC00178238-02
NCGC00178238-01
BPBIO1_000157
PRESTWICK3_000191
AB00053715
midodrine
42794-76-3
C07890
dl-n1-(beta-hydroxy-2,5-dimethoxyphenethyl)glycinamid
DB00211
2-amino-n-(2,5-dimethoxy-beta-hydroxyphenethyl)acetamide
midodrin
1-(2',5'-dimethoxyphenyl)-2-glycinamidoethanol
(+/-)-2-amino-n-(beta-hydroxy-2,5-dimethoxyphenethyl)acetamide
BSPBIO_000141
IDI1_000955
acetamide, 2-amino-n-(2-(2,5-dimethoxyphenyl)-2-hydroxyethyl)-
(rs)-n'-(beta-hydroxy-2,5-dimethoxy-phenethyl)glycinamid
2-amino-n-(2,5-dimethoxy-beta-hydroxyphenethylacetamide
midodrinum [inn-latin]
midodrine [inn:ban]
midodrina [inn-spanish]
2-amino-n-(2,5-dimethoxy-beta-hydroxyphenethyl)acetamid
einecs 255-945-3
st 1085
st-1085 ,
KBIO2_002121
KBIO2_007257
KBIO2_004689
KBIO3_002650
KBIOSS_002121
KBIOGR_000763
PRESTWICK0_000191
SPECTRUM3_001585
PRESTWICK1_000191
SPBIO_002062
SPECTRUM2_001545
SPBIO_001390
SPECTRUM4_000192
NINDS_000955
PRESTWICK2_000191
SPECTRUM5_000962
midodrine (inn)
D08220
2-amino-n-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]acetamide
CHEMBL1201212
133163-28-7
AKOS015967099
hsdb 7854
unii-6ye7pbm15h
6ye7pbm15h ,
97476-58-9
S5735
2-amino-n-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]ethanimidic acid
gtpl7240
midodrine [hsdb]
(+/-)-2-amino-n-(.beta.-hydroxy-2,5-dimethoxyphenethyl)acetamide
midodrine [inn]
acetamide, 2-amino-n-(2-(2,5-dimethoxyphenyl)-2-hydroxyethyl)-, (+/-)-
midodrine [vandf]
midodrine [who-dd]
midodrine [mi]
SCHEMBL131436
CS-4688
HY-12749
AB00053715_08
SCHEMBL20996761
DTXSID0023321 ,
SBI-0051934.P002
2-amino-n-(2-(2,5-dimethoxyphenyl)-2-hydroxyethyl)acetamide
FT-0740719
Q415051
PTKSEFOSCHHMPD-UHFFFAOYSA-N
BRD-A79981887-003-09-9
midodrine free base
HMS3886M20
42794-76-3 (free base)
A913477
EN300-25893675
rac-n-(2-(2,5-dimethoxyphenyl)-2-hydroxyethyl)glycinamide
midodrina (inn-spanish)
midodrinum (inn-latin)
rs)-n'-(beta-hydroxy-2,5-dimethoxy-phenethyl)glycinamid
dtxcid903321
einecs (255-945-3)
c01ca17

Research Excerpts

Overview

Midodrine is an orally administered vasopressor which is commonly used off-label to expedite weaning from vasopression infusions. methylene blue is an intravenously administered blue dye used to restore vascular tone and increase blood pressure.

ExcerptReferenceRelevance
"Midodrine is an oral α 1-adrenergic receptor agonist that offers a potential means of liberating patients from IV vasopressor therapy."( Putting midodrine on the MAP: An approach to liberation from intravenous vasopressors in vasodilatory shock.
Floris, LM; Hawkins, WA; Patterson, JM; Peters, NA; Smith, SE, 2022
)
1.88
"Midodrine is an orally administered vasopressor which is commonly used off-label to expedite weaning from vasopressor infusions and facilitate discharge from ICU."( Oral midodrine does not expedite liberation from protracted vasopressor infusions: A case-control study.
Anstey, MH; Jacques, A; Palmer, RN; Rauniyar, R; Wibrow, B; Wood, AJ, 2023
)
2.15
"Midodrine is an orally administered alpha-1 adrenergic agonist while methylene blue is an intravenously administered blue dye used to restore vascular tone and increase blood pressure."( Clinical utility of midodrine and methylene blue as catecholamine-sparing agents in intensive care unit patients with shock.
Sullivan, JB; Tchen, S, 2020
)
1.6
"Midodrine is an oral alpha-1 adrenergic agonist approved for treatment of symptomatic orthostatic hypotension."( Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial).
Anstey, MH; Chhangani, K; DiBiasio, A; Eikermann, M; Levine, A; Ng, PY; Roberts, B; Sarge, T; Thevathasan, T; Wibrow, B, 2017
)
2.62
"Midodrine is an oral, peripherally acting alpha-adrenergic agonist. "( The Role of Midodrine for Hypotension Outside of the Intensive Care Unit.
Gutman, LB; Wilson, BJ, 2017
)
2.28
"Midodrine is an oral alpha-agonist approved for orthostatic hypotension. "( Trends in Use of Midodrine in the ICU: A Single-Center Retrospective Case Series.
Andrijasevic, N; Gajic, O; Kashyap, R; Lin, E; Nasim, F; Rizvi, MS; Trivedi, V, 2018
)
2.26
"Midodrine is an α1-agonist approved for orthostatic hypotension. "( Continuation of Newly Initiated Midodrine Therapy After Intensive Care and Hospital Discharge: A Single-Center Retrospective Study.
Barreto, EF; Gajic, O; Mara, KC; Nei, AM; Rizvi, MS, 2019
)
2.24
"Midodrine is an α1 vasoconstrictor commonly used for the treatment of pulmonary arterial hypertension (PAH) and intradialytic hypotension."( Midodrine treatment in a patient with treprostinil-induced hypotension receiving hemodialysis.
Alobaidi, A; Bielnicka, P; Drambarean, B, 2019
)
2.68
"Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension. "( Clinical study on the therapeutic role of midodrine in non azotemic cirrhotic patients with tense ascites: a double-blind, placebo-controlled, randomized trial.
Al-Garem, N; Ali, A; Amin, M; Farid, S; Kassem, M, 2014
)
2.11
"Midodrine (MD) is a prodrug that is converted after oral administration to Desglymidodrine (DMD). "( Development and validation of LC-MS/MS assay for the determination of the prodrug Midodrine and its active metabolite Desglymidodrine in plasma of ascitic patients: Application to individualized therapy and comparative pharmacokinetics.
Al-Ghobashy, MA; Ali, AA; Farid, SF; Kassem, MA, 2015
)
2.09
"Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension, and can also be used for hepatorenal syndrome and cirrhotic patients with tense ascites. "( Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers.
Al-Garem, N; Al-Ghobashy, M; Ali, A; Amin, M; Farid, S; Kassem, M, 2016
)
2.14
"Midodrine hydrochloride is a short-acting pressor agent that raises blood pressure in the upright position in patients with orthostatic hypotension. "( Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study.
Martin, P; Much, D; Robinson, AG; Smith, W; Wan, H, 2016
)
2.2
"Midodrine is a well-tolerated and clinically effective treatment for symptomatic orthostatic hypotension."( Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study.
Martin, P; Much, D; Robinson, AG; Smith, W; Wan, H, 2016
)
2.2
"Midodrine is an alpha-agonist that causes peripheral vasoconstriction, resulting in increased blood pressure. "( Midodrine-induced vascular ischemia in a hemodialysis patient: a case report and literature review.
Haimov, M; Ross, MJ; Rubinstein, S, 2008
)
3.23
"Midodrine is an alpha-agonist prodrug of desglymidodrine (DGM) that has been reported to be of clinical benefit in patients with neurocardiogenic syncope. "( Pharmacokinetic and pharmacodynamic effects of midodrine on blood pressure, the autonomic nervous system, and plasma natriuretic peptides: a prospective, randomized, single-blind, two-period, crossover, placebo-controlled study.
Champlain, Jd; Lamarre-Cliche, M; Larochelle, P; Souich, Pd, 2008
)
2.05
"Midodrine is a pro-drug whose primary metabolite is an alpha-1 adrenoreceptor agonist."( Rationale for the prevention of syncope trial IV: assessment of midodrine.
Faris, PD; McRae, M; Raj, SR; Sheldon, RS, 2012
)
1.34
"Midodrine hydrochloride is an important therapeutic option for children with POTS. "( Midregional pro-adrenomedullin as a predictor for therapeutic response to midodrine hydrochloride in children with postural orthostatic tachycardia syndrome.
Chen, L; Du, J; Jin, H; Li, X; Liao, Y; Ochs, T; Tang, C; Zhang, F, 2012
)
2.05
"Midodrine hydrochloride is a peripheral alpha(1)-adrenoreceptor agonist that induces venous and arterial vasoconstriction. "( Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent.
Bossù, E; Desideri, N; Donati, E; Farina, A; Palmery, M; Quaglia, MG; Strano, S, 2004
)
2.07
"Midodrine is an oral alpha-1 agonist that has been used in several small studies to prevent intradialytic hypotension (IDH)."( Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review.
Garg, AX; Heidenheim, AP; House, AA; Prakash, S, 2004
)
2.49
"Midodrine is an oral drug for orthostatic hypotension. "( Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives.
Fujii, N; Inui, K; Irie, M; Katsura, T; Niida, A; Terada, T; Tomita, K; Tsuda, M, 2006
)
2
"Midodrine is a peripheral, selective alpha1-adrenergic agonist that causes arterial and venous vasoconstriction."( Orthostatic hypotension: evaluation and treatment.
Magnino, C; Maule, S; Naso, D; Papotti, G; Testa, E; Veglio, F, 2007
)
1.06
"Midodrine hydrochloride is a potent peripherally-acting alpha1 agonist that is well absorbed and rapidly metabolized to its active metabolite. "( Prolonged supine hypertension due to midodrine use in an orthostatic hypotensive child.
Olgar, S; Omeroglu, RE,
)
1.85
"Midodrine is a safe and efficient adjunct to penile vibratory stimulation for anejaculation in spinal cord injured patients."( Midodrine improves ejaculation in spinal cord injured men.
Chartier-Kastler, E; Denys, P; Plante, P; Previnaire, JG; Soler, JM, 2007
)
3.23
"Midodrine is an alpha-one agonist that produces arterial and venous constriction and leads to a decrease in heart rate by baroreceptor reflexes."( A comparison of postspace-flight orthostatic intolerance to vasovagal syncope and autonomic failure and the potential use of the alpha agonist midodrine for these conditions.
Jankovic, J; McElligott, MA; Piwinski, SE, 1994
)
1.21
"Midodrine hydrochloride is an alpha-mimetic drug acting directly on the peripheral alpha-receptor and increases blood pressure."( Midodrine hydrochloride in patients on hemodialysis with chronic hypotension.
Fang, JT; Huang, CC, 1996
)
2.46
"Oral midodrine appears to be a safe and effective therapy for the treatment of hemodialysis hypotension."( Midodrine treatment for patients with hemodialysis hypotension.
Caruso, FS; Flynn, JJ; McElligott, MA; Mitchell, MC, 1996
)
2.19
"Midodrine is a prodrug which undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration. "( Midodrine. A review of its therapeutic use in the management of orthostatic hypotension.
McClellan, KJ; Wilde, MI; Wiseman, LR, 1998
)
3.19
"Midodrine is a peripherally acting alpha-adrenergic agonist useful in the treatment of NOH. "( A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension.
Kaufmann, HC; Low, PA; McElligott, MA; Opfer-Gehrking, TL; Perera, R; Sheng, KN; Wright, RA, 1998
)
2.01
"Midodrine appears to be an effective and safe treatment for HD patients with symptomatic IDH, and remains beneficial when used for an extended period of time."( Midodrine is effective and safe therapy for intradialytic hypotension over 8 months of follow-up.
Brickel, HM; Cruz, DN; Mahnensmith, RL; Perazella, MA, 1998
)
2.46
"Midodrine is a potent and selective alpha1-receptor agonist and its potential to increase urethral closure pressure could be useful in the treatment of female stress incontinence. "( Randomized double-blind placebo-controlled multicenter evaluation of efficacy and dose finding of midodrine hydrochloride in women with mild to moderate stress urinary incontinence: a phase II study.
Abbühl, BE; Dijkman, GA; Eerdmans, PH; Egarter, C; Feyereisl, J; Heidler, H; Kölle, D; Plasman, JE; Schmidbauer, C; Tamussino, K; Vierhout, ME; Weil, EH; Wein, W, 1998
)
1.96
"Midodrine is an oral agent which acts as a selective peripherally-acting alpha-receptor agonist. "( Midodrine: a selective alpha-adrenergic agonist for orthostatic hypotension and dialysis hypotension.
Cruz, DN, 2000
)
3.19
"Midodrine is an orally active adrenergic agonist useful in the treatment of hypotension. "( Pharmacodynamics of midodrine, an antihypotensive agent.
Bloedow, DC; Fealey, RD; Moyer, TP; Schirger, A; Sheps, SG; Zachariah, PK, 1986
)
2.04

Effects

Midodrine has been used as an oral agent for haemodynamic support in patients with orthostatic hypotension or cirrhosis. Midodrine and tolvaptan have been used separately in these patients.

ExcerptReferenceRelevance
"Midodrine has been used as an oral agent for haemodynamic support in patients with orthostatic hypotension or cirrhosis."( Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis.
Bagshaw, SM; Fiest, K; Kamaleldin, M; Karvellas, CJ; Kilcommons, S; Kutsogiannis, J; Lau, V; MacIntyre, E; Opgenorth, D; Rewa, OG; Rochwerg, B; Senaratne, J; Slemko, J; Sligl, W; Wang, X, 2022
)
2.89
"Midodrine has shown promising results in the treatment of AKI-hepatorenal syndrome (HRS-AKI)."( Midodrine and albumin versus albumin alone for the secondary prophylaxis of acute kidney injury in a patient with cirrhosis and ascites.
Arora, A; Bansal, N; Kumar, A; Puri, P; Sharma, P; ShriHari, AA; Singla, V, 2021
)
2.79
"Midodrine has been proposed in the management of patients with these conditions but its impact on patient important outcomes remains uncertain."( Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review.
Catalano, HN; González Malla, C; Guyatt, G; Izcovich, A; Manzotti, M, 2014
)
2.57
"Midodrine has demonstrated usefulness in hepatorenal syndrome."( Clinical study on the therapeutic role of midodrine in non azotemic cirrhotic patients with tense ascites: a double-blind, placebo-controlled, randomized trial.
Al-Garem, N; Ali, A; Amin, M; Farid, S; Kassem, M, 2014
)
1.39
"Midodrine has been reported to improve systemic and renal hemodynamics in patients with cirrhotic ascites. "( Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis.
Cheng, G; Guo, TT; Liu, ZX; Ren, Y; Song, Y; Yang, Y, 2016
)
2.27
"Midodrine and tolvaptan have been used separately in these patients."( Midodrine and tolvaptan in patients with cirrhosis and refractory or recurrent ascites: a randomised pilot study.
Bhalla, A; Rai, N; Sharma, N; Singh, A; Singh, B; Singh, V; Vijayvergiya, R, 2017
)
2.62
"Midodrine has recently become the only licenced medication for OH in the UK."( New Horizons in orthostatic hypotension.
Frith, J; Parry, SW, 2017
)
1.18

Actions

Oral midodrine does not increase the natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. Midodrine did not cause any untoward reactions in subjects before or after flight.

ExcerptReferenceRelevance
"Oral midodrine does not increase the natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. "( The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascites.
Chalasani, N; Hamman, M; Jones, D; Kahi, C; Kwo, PY; Misra, VL; Vuppalanchi, R, 2010
)
1.23
"Midodrine did not cause any untoward reactions in these subjects before or after flight; in fact, a modest beneficial effect was seen on postflight tachycardia (p = 0.036)."( Hemodynamic effects of midodrine after spaceflight in astronauts without orthostatic hypotension.
Meck, JV; Platts, SH; Waters, WW; Ziegler, MG, 2006
)
1.37
"Oral midodrine may further increase ejaculation success, while maintaining autonomy."( Perceived physiological and orgasmic sensations at ejaculation in spinal cord injured men.
Bélanger, M; Charvier, K; Côté, I; Courtois, F; Fournier, C; Jacquemin, G; Leriche, A; Raymond, D; Vézina, JG, 2008
)
0.8
"Midodrine did not cause any change in the quality of diabetic control nor any significant alteration in serum lipid or uric acid levels."( [Investigations of the effect of midodrine on carbohydrate and fat metabolism with particular reference to the diabetic metabolic state (author's transl)].
Brändle, J; Irsigler, K; Lageder, H, 1977
)
1.26

Treatment

Midodrine treatment, directed at the autonomic nervous system, resulted in correction of the dysautonomia followed by improvement of fatigue. Treatment with midodrine, 10 mg, was associated with elevated systolic blood pressure during peak exercise in 3 participants.

ExcerptReferenceRelevance
"Midodrine treatment was stopped and the patient was treated with intravascular rehydration and furosemide. "( Case report: severe myoclonus associated with oral midodrine treatment for hypotension.
Chen, M; Ling, B; Ren, Y; Song, F; Wu, J; Wu, S; Xuan, Z; Ye, X; Zhang, H, 2020
)
2.25
"Midodrine treatment was associated with an increase in the magnitude of decline of the IV vasopressor rate. "( Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions.
Ball, SA; Berg, S; Bittner, EA; Eikermann, M; Kalman, R; Levine, AR; Meyer, MJ; Ryan, C; Stanislaus, AB, 2013
)
2.35
"Midodrine may have treatment effects on cirrhotic ascites. "( Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis.
Cheng, G; Guo, TT; Liu, ZX; Ren, Y; Song, Y; Yang, Y, 2016
)
2.27
"Midodrine treatment, directed at the autonomic nervous system, resulted in correction of the dysautonomia followed by improvement of fatigue."( Midodrine treatment for chronic fatigue syndrome.
Dreyfuss, D; Naschitz, J; Rosner, I; Yeshurun, D, 2004
)
2.49
"Midodrine treatment improved the frequency of the ability to stand as compared with ephedrine, and was associated with a significantly higher incidence of standing systolic pressures > 80 mm Hg than was placebo (P < 0.001)."( Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension.
Fouad-Tarazi, FM; Goren, H; Okabe, M, 1995
)
1.01
"Midodrine treatment also significantly increased postdialysis systolic and diastolic blood pressures from baseline values of 90.8 +/- 3.8 and 58.3 +/- 3.0 mm Hg to 113.3 +/- 7.1 and 70.6 +/- 3.1 mm Hg (p < 0.01 and p < 0.01 respectively)."( Midodrine for the treatment of intradialytic hypotension.
Li, HP; Lim, PS; Lim, YT; Yang, CC; Yeh, CH, 1997
)
2.46
"Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs."( Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial.
Ariza, X; Castellote, J; Colmenero, J; Córdoba, J; de Prada, G; Fabrellas, N; Garcia-Martínez, R; Ginès, P; Graupera, I; Guevara, M; Huelin, P; Lopez Benaiges, E; Manríquez, M; Márquez, F; Martín-Llahí, M; Moreira, R; Navasa, M; Nazar, A; Pavesi, M; Pose, E; Simón-Talero, M; Solà, E; Solé, C; Suñé, P; Torrens, M; Vargas, V; Ventura, M; Xiol, X, 2018
)
2.26
"Treatment with midodrine, 10 mg, was associated with elevated systolic blood pressure during peak exercise in 3 participants. "( Double-blinded, placebo-controlled trial of midodrine for exercise performance enhancement in tetraplegia: a pilot study.
Birk, CA; Birk, TJ; Hinderer, SR; Nieshoff, EC; Yavuzer, G, 2004
)
0.94

Toxicity

Midodrine, an oral peripheral alpha-1 adrenergic agonist, is an effective and safe therapy for symptomatic IDH. Six of 10 studies report improvement in symptoms of IDH, and there were no reported serious adverse events ascribed to midodrine.

ExcerptReferenceRelevance
" However, recent studies have shown that midodrine, an oral peripheral alpha-1 adrenergic agonist, is an effective and safe therapy for symptomatic IDH in the short-term."( Midodrine is effective and safe therapy for intradialytic hypotension over 8 months of follow-up.
Brickel, HM; Cruz, DN; Mahnensmith, RL; Perazella, MA, 1998
)
2.01
" This medication has been demonstrated to be effective and safe in the acute and chronic treatment of haemodialysis-associated hypotension in end stage renal disease patients."( Efficacy and safety of midodrine in the treatment of dialysis-associated hypotension.
Perazella, MA, 2003
)
0.63
" Six of 10 studies report improvement in symptoms of IDH, and there were no reported serious adverse events ascribed to midodrine."( Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review.
Garg, AX; Heidenheim, AP; House, AA; Prakash, S, 2004
)
1.97
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004
)
0.32
" Adverse events are mostly cardiovascular and related to vasoconstriction."( Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome.
Bendtsen, F; Borup, T; Krag, A; Møller, S, 2008
)
0.35

Pharmacokinetics

The pharmacokinetic characteristics of the prodrug midodrine and the active metabolite de-glymidodrine in this patient with end-stage renal disease approximate those reported for patients with normal renal function.

ExcerptReferenceRelevance
" The pharmacokinetic characteristics of the prodrug midodrine and the active metabolite de-glymidodrine in this patient with end-stage renal disease approximate those reported for patients with normal renal function."( Midodrine efficacy and pharmacokinetics in a patient with recurrent intradialytic hypotension.
Balfe, JW; Blowey, DL; Gajaria, MM; Gupta, I; Koren, G, 1996
)
1.99
" In this paper, a joined in vitro/in silico-in vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic (PBPK) modeling approach is presented to predict active drug exposure in human after oral prodrug administration."( Predicting human exposure of active drug after oral prodrug administration, using a joined in vitro/in silico-in vivo extrapolation and physiologically-based pharmacokinetic modeling approach.
Malmborg, J; Ploeger, BA,
)
0.13
"Physico-chemical and in vitro assays as well as in silico predictions were proposed to characterize key pharmacokinetic properties (e."( Predicting human exposure of active drug after oral prodrug administration, using a joined in vitro/in silico-in vivo extrapolation and physiologically-based pharmacokinetic modeling approach.
Malmborg, J; Ploeger, BA,
)
0.13
" The applicability of the assay for the determination of the pharmacokinetic parameters of MD and DMD and personalized therapy was demonstrated in healthy volunteers and ascitic patients."( Development and validation of LC-MS/MS assay for the determination of the prodrug Midodrine and its active metabolite Desglymidodrine in plasma of ascitic patients: Application to individualized therapy and comparative pharmacokinetics.
Al-Ghobashy, MA; Ali, AA; Farid, SF; Kassem, MA, 2015
)
0.64
" The objective of the present work was to study the clinical pharmacokinetic parameters of midodrine and its active metabolite desglymidodrine in cirrhotic patients with tense ascites, which may help in dose selection and improve treatment outcome."( Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers.
Al-Garem, N; Al-Ghobashy, M; Ali, A; Amin, M; Farid, S; Kassem, M, 2016
)
0.92
" Based on the results of the pharmacokinetic analysis, the patient group was further subdivided into those receiving the interacting drug ranitidine (five patients) and those not receiving the interacting drug (seven patients)."( Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers.
Al-Garem, N; Al-Ghobashy, M; Ali, A; Amin, M; Farid, S; Kassem, M, 2016
)
0.7

Bioavailability

Midodrine hydrochloride is a potent peripherally-acting alpha1 agonist. It is well absorbed and rapidly metabolized to its active metabolite. Midodrine is a prodrug that is almost completely absorbed after oral administration.

ExcerptReferenceRelevance
" The data of 10 volunteers could be used for the calculations of the bioavailability of ST 1059 by the AUC."( [The bioavailability of midodrin and alpha-2,5-dimethoxyphenyl-beta-aminoethanol hydrochloride].
Grobecker, H; Kees, F; Linden, M; Schrader, E; Welte, S, 1987
)
0.27
" Midodrine is a prodrug that is almost completely absorbed after oral administration and converted into its active drug de-glymidodrine in the systematic circulation, with a bioavailability of 93%."( Midodrine: a selective alpha-adrenergic agonist for orthostatic hypotension and dialysis hypotension.
Cruz, DN, 2000
)
2.66
" The intestinal H+-coupled peptide transporter 1 (PEPT1) transports various peptide-like drugs and has been used as a target molecule for improving the intestinal absorption of poorly absorbed drugs through amino acid modifications."( Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives.
Fujii, N; Inui, K; Irie, M; Katsura, T; Niida, A; Terada, T; Tomita, K; Tsuda, M, 2006
)
0.55
"Midodrine hydrochloride is a potent peripherally-acting alpha1 agonist that is well absorbed and rapidly metabolized to its active metabolite."( Prolonged supine hypertension due to midodrine use in an orthostatic hypotensive child.
Olgar, S; Omeroglu, RE,
)
1.85

Dosage Studied

No difference in the incidence of DGF was observed based on the midodrine dosing regimen. The hypothesis of ephaptic transmission was supported by meaningful decrease of muscle sympathetic activity detected by microneurography before and after the dosage of L-DOPS.

ExcerptRelevanceReference
" The most commonly experienced adverse effects--piloerector reactions, gastrointestinal disorders, and cardiovascular complaints--are generally mild and can be controlled by reducing the dosage of midodrine."( Midodrine. A review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders.
Goa, KL; McTavish, D, 1989
)
1.91
"5 mg midodrine tablets and dosage was adjusted according to each patient's condition."( Controlled clinical investigation of dimetophrine versus midodrine in the management of moderately decreased arterial blood pressure.
Cecchi, A; Marini, U; Venturini, M, 1984
)
1.03
" After adjustment of dosage over 2 to 4 weeks, patients were followed-up clinically."( Efficacy of midodrine hydrochloride in neurocardiogenic syncope refractory to standard therapy.
Akhtar, M; Biehl, M; Blanck, Z; Deshpande, S; Dhala, A; Jazayeri, MR; Maglio, C; Sra, J, 1997
)
0.68
" The hypothesis of ephaptic transmission was supported by meaningful decrease of muscle sympathetic activity detected by microneurography before and after the dosage of L-DOPS, which effectively suppressed the pain as well as other alpha-stimulant, midodrine hydrochloride."( [Pain caused by ephaptic transmission occurring in the recovery phase of diabetic vascular mononeuropathy was effectively suppressed with L-threo-3,4-dihydroxyphenyl-serine].
Inoue, K; Kunimoto, M; Ohshima, F, 1998
)
0.48
" However, neither the most effective dosage of midodrine nor the required frequency of administration is established."( A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension.
Kaufmann, HC; Low, PA; McElligott, MA; Opfer-Gehrking, TL; Perera, R; Sheng, KN; Wright, RA, 1998
)
0.83
" There was a significant linear relation between midodrine dosage and mean systolic blood pressure."( A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension.
Kaufmann, HC; Low, PA; McElligott, MA; Opfer-Gehrking, TL; Perera, R; Sheng, KN; Wright, RA, 1998
)
0.82
" Second, dose-response curves to increasing doses (1-512ng/min) of noradrenaline infused locally to the dorsal hand vein were determined using a linear variable differential transformer."( Effect of amezinium metilsulfate on the finger skin vasoconstrictor response to cold stimulation and venoconstrictor response to noradrenaline.
Fujimura, A; Harada, K; Ohashi, K; Ohmori, M, 1998
)
0.3
" Midodrine and octreotide were dosed to obtain a stable increase of at least 15 mm Hg of mean arterial pressure."( Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide.
Amodio, P; Angeli, P; Caregaro, L; Craighero, R; Gatta, A; Gerunda, G; Maffei-Faccioli, A; Merenda, R; Roner, P; Sticca, A; Volpin, R, 1999
)
1.45
" These preliminary results suggest that midodrine is safe and effective in transplant recipients; however, the dosage should be titrated to symptomatic relief or a maximum dose of 30 mg."( Preliminary experience with midodrine in kidney/pancreas transplant patients with orthostatic hypotension.
Alloway, RR; Gaber, AO; Hurst, GC; Somerville, KT; Stratta, RJ, 2000
)
0.87
"Prospective dose-response trial."( Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia.
Bauman, WA; Handrakis, JP; Radulovic, M; Rosado-Rivera, D; Wecht, JM, 2010
)
0.75
" 10 miRNAs were commonly altered in serum from dopamine and either fenoldopam or midodrine dosed rats; 18 of these 102 were also altered in mesenteries from rats with drug-induced vascular injury, suggesting their possible utility as peripheral biomarkers."( MicroRNA changes in rat mesentery and serum associated with drug-induced vascular injury.
Chau, NT; Frazier, KS; Mirabile, RC; Scicchitano, MS; Thomas, HC; Thomas, RA, 2012
)
0.61
" Therefore, elevation of the bed of the head and dosing of short-acting antihypertensive agents at bedtime is often indicated."( Orthostatic hypotension associated with baroreceptor dysfunction: treatment approaches.
Bakris, GL; Briasoulis, A; Silver, A; Yano, Y, 2014
)
0.4
" Future developments in dosage and administrative techniques for terlipressin may have an important role to play in maintaining clinical efficacy whilst improving tolerability in the management of HRS."( Hepatorenal syndrome: the clinical impact of vasoactive therapy.
Colle, I; Laterre, PF, 2018
)
0.48
" No difference in the incidence of DGF was observed based on the midodrine dosing regimen."( Influence of pretransplant midodrine use on outcomes after kidney transplantation.
Brennan, DC; Gharabagi, A; Hagopian, JC; Horwedel, TA; Pottebaum, AA, 2018
)
1.02
" Future investigation into standardized initiation of midodrine at an adequate dosage with an expedited titration strategy is needed in order to assess the utility of this strategy in shock management."( Midodrine as an Adjuvant to Intravenous Vasopressor Agents in Adults With Resolving Shock: Systematic Review and Meta-Analysis.
Balk, RA; Hammond, DA; Menich, BE; Peksa, GD; Smith, MN; Trivedi, AP, 2020
)
2.25
" The safety of midodrine dosing at greater than 30 mg daily has not been established to date."( Midodrine treatment in a patient with treprostinil-induced hypotension receiving hemodialysis.
Alobaidi, A; Bielnicka, P; Drambarean, B, 2019
)
2.31
" Because of the variety of dosing strategies used and the incongruences between patient populations, it is also challenging to define finite recommendations."( Clinical utility of midodrine and methylene blue as catecholamine-sparing agents in intensive care unit patients with shock.
Sullivan, JB; Tchen, S, 2020
)
0.88
" Study medication was taken 2 or 3 times/day, depending on their sleep/wake schedule, BP, and any related symptoms were recorded before and 1 h after each dosage and periodically throughout the day."( Clinical trial of home blood pressure monitoring following midodrine administration in hypotensive individuals with spinal cord injury.
Bauman, WA; Dyson-Hudson, TA; Katzelnick, CG; Kirshblum, SC; Wecht, JM; Weir, JP, 2023
)
1.15
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (4)

RoleDescription
prodrugA compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
alpha-adrenergic agonistAn agent that selectively binds to and activates alpha-adrenergic receptors.
sympathomimetic agentA drug that mimics the effects of stimulating postganglionic adrenergic sympathetic nerves. Included in this class are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.
vasoconstrictor agentDrug used to cause constriction of the blood vessels.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
secondary alcoholA secondary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has two other carbon atoms attached to it.
amino acid amideAn amide of an amino acid formed formally by conversion of the carboxy group to a carboxamido group.
aromatic etherAny ether in which the oxygen is attached to at least one aryl substituent.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (31)

Assay IDTitleYearJournalArticle
AID588215FDA HLAED, alkaline phosphatase increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID588218FDA HLAED, lactate dehydrogenase (LDH) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588214FDA HLAED, liver enzyme composite activity2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588216FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID678717Inhibition of human CYP3A4 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 7-benzyloxyquinoline as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID588219FDA HLAED, gamma-glutamyl transferase (GGT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID678712Inhibition of human CYP1A2 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using ethoxyresorufin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID678713Inhibition of human CYP2C9 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 7-methoxy-4-trifluoromethylcoumarin-3-acetic acid as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID588217FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID678721Metabolic stability in human liver microsomes assessed as GSH adduct formation at 100 uM after 90 mins by HPLC-MS analysis2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID678722Covalent binding affinity to human liver microsomes assessed per mg of protein at 10 uM after 60 mins presence of NADPH2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678716Inhibition of human CYP3A4 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using diethoxyfluorescein as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678715Inhibition of human CYP2D6 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 4-methylaminoethyl-7-methoxycoumarin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678714Inhibition of human CYP2C19 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 3-butyryl-7-methoxycoumarin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (496)

TimeframeStudies, This Drug (%)All Drugs %
pre-199048 (9.68)18.7374
1990's67 (13.51)18.2507
2000's141 (28.43)29.6817
2010's168 (33.87)24.3611
2020's72 (14.52)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 109.75

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index109.75 (24.57)
Research Supply Index6.47 (2.92)
Research Growth Index4.85 (4.65)
Search Engine Demand Index201.78 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (109.75)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials118 (22.43%)5.53%
Reviews85 (16.16%)6.00%
Case Studies102 (19.39%)4.05%
Observational4 (0.76%)0.25%
Other217 (41.25%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (77)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase 1 Proof-of-concept Clinical Trial Evaluating the Safety and Tolerability of Midodrine in Hepatopulmonary Syndrome [NCT03600870]Phase 110 participants (Actual)Interventional2018-08-02Completed
[NCT01587222]Phase 20 participants (Actual)Interventional2016-07-31Withdrawn(stopped due to the sponsor did not provide the treatment)
Impact of Midodrine Administration on the Clinical Outcome of Septic Shock Patients [NCT03911817]Phase 460 participants (Actual)Interventional2017-11-15Completed
Treatment of Orthostatic Intolerance in Patients With Parkinson's Disease Using Midodrine [NCT02365012]50 participants (Anticipated)Interventional2014-04-30Recruiting
Midodrine as Novel Treatment of Post-Cardiopulmonary Bypass Vasoplegic Syndrome [NCT04668859]Phase 410 participants (Actual)Interventional2016-07-29Terminated(stopped due to PI relocated)
Mechanism and the Effect of Midodrine on Portal Pressures in Patients With Cirrhosis [NCT01331785]0 participants (Actual)Interventional2011-04-30Withdrawn(stopped due to Lack of enrollment)
To Study the Safety and Efficacy of Midodrine With Albumin Versus Albumin Alone in Hepatic Hydrothorax- A Pilot Randomised Controlled Trial [NCT03645642]8 participants (Actual)Interventional2018-09-30Completed
Effect of Cardioneuroablation vs Midodrine on Syncope Recurrence Among Patients With Vasovagal Syncope: The CAMPAIGN Randomized Clinical Trial [NCT05803148]184 participants (Anticipated)Interventional2023-04-05Recruiting
Midodrine Plus Albumin Versus Midodrine Alone to Prevent Cirrhosis Related Complications in Children With Cirrhosis and Ascites - An Open Label Randomized Controlled Trial. [NCT06091345]60 participants (Anticipated)Interventional2023-10-25Not yet recruiting
Efficacy of Albumin Plus Midodrine v/s Albumin Alone in Reducing Incidence of Paracentesis Induced Circulatory Dysfunctions in ACLF Patients-A Randomized Controlled Trial. [NCT04474262]150 participants (Anticipated)Interventional2020-07-15Not yet recruiting
Midodrine and Albumin for Cirrhotic Patients in the Waiting List for Liver Transplantation [NCT00839358]Phase 4199 participants (Actual)Interventional2008-08-31Completed
Effect of Midodrine on HVPG in Advanced Chronic Liver Disease - A Pilot Study [NCT04455464]60 participants (Actual)Interventional2020-07-11Completed
"Evaluation of Albumin and Midodrine Versus Albumin Alone in Outcome of Refractory Ascites in Patients With Decompensated Cirrhosis - A Double Blind Randomized Controlled Trial." [NCT04816240]200 participants (Anticipated)Interventional2021-05-15Recruiting
Oral Midodrine Hydrochloride in Early Sepsis: Randomized, Double Blind and Placebo-Controlled Feasibility Study [NCT03129542]Phase 133 participants (Actual)Interventional2017-08-30Completed
Safety and Efficacy of Midodrine Hydrochloride in the Management of Refractory Ascites Due to Cirrhosis in Children: a Pilot Study [NCT04043858]20 participants (Anticipated)Interventional2020-06-05Recruiting
Role of Midodrine and Tolvaptan in Patients With Cirrhosis With Refractory or Recurrent Ascites [NCT02173288]Phase 2/Phase 350 participants (Actual)Interventional2013-07-31Completed
Effect of Administration of Intravenous Albumin and Oral Midodrine on Renal Function in Patients With Cirrhosis and Functional Renal Impairment [NCT01133795]Phase 27 participants (Actual)Interventional2010-02-28Completed
Single-Dose Food In Vivo Bioequivalence Study of Midodrine HCl Tablets (5 mg; Mylan) and ProAmatine® Tablets (5 mg; Roberts) in Healthy Volunteers [NCT00650013]Phase 123 participants (Actual)Interventional2002-07-31Completed
Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome (HRS): An Open Multicentric Randomized Study [NCT00742339]Phase 2/Phase 349 participants (Actual)Interventional2005-05-31Terminated(stopped due to Decision of independent monitoring committee: Risk of non-response to treatment significantly higher in midodrine group than in terlipressin group.)
Efficacy and Safety of Midodrine in Refractory or Recurrent Ascites in Children With Cirrhosis - A Randomized Controlled Trial [NCT05084534]20 participants (Anticipated)Interventional2021-11-01Recruiting
Clinical Study Evaluating the Efficacy and Safety of Adjunctive Use of Midodrine in Septic Shock Patients [NCT05778838]Phase 4100 participants (Anticipated)Interventional2023-04-01Recruiting
Vasoconstrictors as Alternatives to Albumin After Large Volume Paracentesis in Cirrhosis [NCT00108355]Phase 429 participants (Actual)Interventional2003-12-31Completed
Treatment of Post-SCI Hypotension: A Randomized Controlled Study of Usual Care Versus Anti Hypotension Therapy [NCT02919917]Phase 2/Phase 366 participants (Actual)Interventional2017-06-01Completed
The Effects of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive Individuals With Spinal Cord Injury [NCT02893553]Phase 241 participants (Actual)Interventional2016-12-31Completed
Effect of Midodrine vs Abdominal Compression on Cardiovascular Risk Markers in Autonomic Failure Patients [NCT04620382]Early Phase 131 participants (Anticipated)Interventional2020-11-09Recruiting
Single-Dose Fasting In Vivo Bioequivalence Study of Midodrine HCl Tablets (5 mg; Mylan) and ProAmatine® Tablets (5 mg; Roberts) in Healthy Volunteers [NCT00650364]Phase 138 participants (Actual)Interventional2002-08-31Completed
Single-Dose Food In Vivo Bioequivalence Study of Midodrine HCl Tablets (5 mg; Mylan) and ProAmatine® Tablets (5 mg; Roberts) in Healthy Volunteers [NCT00648440]Phase 136 participants (Actual)Interventional2002-10-31Completed
Treatment of Orthostatic Intolerance [NCT00262470]Phase 1/Phase 2150 participants (Anticipated)Interventional1997-04-30Active, not recruiting
Midodrine Versus Albumin During Large-volume Paracentesis and Its Effect on Paracentesis Induced Circulatory Disturbance in Patients With Acute on Chronic Liver Failure - A Randomized Controlled Trial [NCT05240391]Phase 350 participants (Actual)Interventional2021-02-20Completed
Angiotensin 2 as a Novel Treatment for Hepatorenal Syndrome [NCT04048707]Phase 248 participants (Anticipated)Interventional2021-07-01Not yet recruiting
A Randomized Controlled Trial of Midodrine During Recovery Phase From Septic Shock [NCT02771158]Phase 40 participants (Actual)Interventional2017-08-31Withdrawn(stopped due to Study never started)
Midodrine and Albumin in Patients With Refractory Ascites. A Randomised Controlled Trial. [NCT04621617]Phase 3114 participants (Anticipated)Interventional2020-11-30Not yet recruiting
A Dose Response Trial Using 5 and 10 mg. of Midodrine Hydrochloride to Treat Orthostatic Hypotension in Persons With SCI [NCT00426842]Phase 211 participants (Actual)Interventional2007-01-31Completed
Midodrine for the Early Liberation of Vasopressor Support in the ICU - The LIBERATE Pilot Study [NCT04489589]Phase 420 participants (Actual)Interventional2021-03-22Completed
Induced Hypertension for Acute Ischemic Stroke [NCT00227448]Phase 260 participants Interventional2003-06-30Completed
The Use of Midodrine, Octreotide and Albumin in Refractory Ascites [NCT00240045]Phase 2/Phase 39 participants (Actual)Interventional2005-10-31Completed
Evaluation and Treatment of Autonomic Failure. [NCT00223691]Phase 1389 participants (Actual)Interventional2002-03-31Completed
Use of Accelerometer for Quantification of Neurogenic Orthostatic Hypotension Symptoms [NCT04782830]29 participants (Anticipated)Interventional2021-02-05Recruiting
The Effect of Oral Midodrine Versus Oral Desmopressin Acetate Use for Liberation From IV Noradrenaline in Intensive Care Unit Patients Recovering From Spinal Shock . [NCT04586790]Phase 290 participants (Anticipated)Interventional2020-10-15Recruiting
Comparison of Outcomes With Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS Trial) [NCT04595942]Phase 31,375 participants (Anticipated)Interventional2020-11-19Recruiting
"Efficacy of Combination of Midodrine With Propranolol in Preventing First Bleed in Decompensated Cirrhotics With Severe Ascites: A Randomized Controlled Trial" [NCT04208776]120 participants (Anticipated)Interventional2020-02-04Recruiting
Pros & Cons of Norepinephrine Infusion Versus Midodrine & Octreotide in Patients With Hepatorenal Syndrome Type 1 in Intensive Care Unit. [NCT03455322]Phase 460 participants (Actual)Interventional2018-08-15Completed
An Open Label Trial to Decrease Signs and Symptoms of Orthostatic Hypotension Using Midodrine in Patients With Preserved Cardiac Output (CO) and an Intravenous Fluid Bolus for Patients With Low CO Following Total Hip Arthroplasty [NCT02154243]13 participants (Actual)Interventional2014-06-30Terminated
Midodrine for the Early Liberation From Vasopressor Support in the ICU - The LIBERATE Multi-Site Study [NCT05058612]Phase 4350 participants (Anticipated)Interventional2021-03-22Recruiting
Assessment of Midodrine in the Prevention of Vasovagal Syncope: The Prevention of Syncope Trial IV (Post 4) [NCT01456481]Phase 4134 participants (Actual)Interventional2011-11-30Active, not recruiting
Safety and Efficacy of L-NAME and Midodrine to Increase MAP in Persons With Tetraplegia [NCT00835224]Phase 234 participants (Actual)Interventional2010-05-31Completed
Minimization of Intradialytic Hypotension Using Cardiography-Guided Intervention [NCT03080441]Phase 435 participants (Anticipated)Interventional2016-11-11Enrolling by invitation
Treatment of Orthostatic Hypotension in Individuals With Spinal Cord Injury [NCT05839652]Phase 425 participants (Anticipated)Interventional2023-07-01Not yet recruiting
A Phase IV, Multi-Center, Double-Blind, Parallel Group, Randomized, Placebo-Controlled Study to Assess the Clinical Benefit of Three Doses of Midodrine Hydrochloride (ProAmatine®) in Subjects With Neurogenic Orthostatic Hypotension [NCT00046163]Phase 4150 participants Interventional2002-09-05Terminated(stopped due to Study was terminated due to poor enrollment)
Midodrine for Ischemic Stroke With Penumbra [NCT02383121]0 participants (Actual)Observational2017-05-10Withdrawn(stopped due to Changed study to an observational study)
Neural and Mechanical Baroreflex Sensitivity and Cerebral Blood Flow [NCT01498809]22 participants (Actual)Observational2012-03-31Completed
Midodrine Use in the Recovery Phase of Septic Shock [NCT02990546]Phase 34 participants (Actual)Interventional2017-03-01Terminated(stopped due to Unable to meet enrollment goals)
Efficacy of Midodrine for the Prevention of Orthostatic Hypotension During Early Mobilization After Fast-track Hip Arthroplasty - a Randomized, Placebo Controlled Trial. [NCT01707953]Phase 3120 participants (Anticipated)Interventional2012-10-31Completed
: Oral Midodrine for Prophylaxis Against Post Spinal Anaesthesia Hypotension During Hip Arthroplasty in Elderly Population: A Randomized Controlled Trial [NCT05548985]58 participants (Actual)Interventional2022-10-17Completed
To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation [NCT05287100]35 participants (Actual)Interventional2022-01-01Completed
Randomized, Double-blind, Sham-controlled to Evaluate the Effects of an Automated Abdominal Binder in Improving Orthostatic Tolerance in Autonomic Failure Patients With Disabling Orthostatic Hypotension [NCT03482297]Phase 1/Phase 231 participants (Anticipated)Interventional2018-03-01Recruiting
The Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure Aim 2 of RDCRN (Rare Diseases Clinical Research Network) Project 2 [NCT02897063]Phase 134 participants (Anticipated)Interventional2016-09-30Recruiting
Hemodynamic Mechanisms of Abdominal Compression in the Treatment of Orthostatic Hypotension in Autonomic Failure [NCT02429557]Phase 129 participants (Anticipated)Interventional2015-04-30Recruiting
Midodrine for the Treatment of Refractory Hypotension in Patients Otherwise Ready for Discharge From the ICU [NCT01531959]Phase 3139 participants (Actual)Interventional2012-04-30Completed
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Crossover Study to Assess the Clinical Benefit of Midodrine Hydrochloride in Patients With Neurogenic Orthostatic Hypotension [NCT00046475]Phase 4140 participants (Actual)Interventional1997-12-01Completed
Preoperative Midodrine for Improving Hemodynamics in Orthopedic Patients Undergoing Spinal Anesthesia [NCT04396548]70 participants (Actual)Interventional2020-06-08Completed
[NCT00004268]Phase 2300 participants Interventional2001-04-30Completed
[NCT00004479]0 participants Interventional1999-03-31Completed
Midodrine Use for Hypotension Requiring IV Vasopressor Therapy in Early Septic Shock [NCT03706053]Phase 310 participants (Actual)Interventional2018-11-05Terminated(stopped due to No funding for the study; not enough staff)
Thermoregulation and Cognition During Cool Ambient Exposure in Tetraplegia [NCT02379156]Phase 430 participants (Actual)Interventional2015-04-30Active, not recruiting
A Phase 4, Randomized-withdrawal, Double-blind, Placebo Controlled, Parallel-group Study to Investigate the Clinical Benefit of Midodrine Hydrochloride in Male and Female Subjects With Symptomatic Orthostatic Hypotension [NCT01515865]Phase 498 participants (Actual)Interventional2012-05-23Completed
Randomized Trial Comparing the Efficacy and Safety of Terlipressin With Albumin Versus Midodrine With Albumin Versus Albumin Alone in Prevention of Paracentesis Induced Circulatory Dysfunction in Cirrhosis [NCT03144713]150 participants (Actual)Interventional2017-05-28Completed
RANDOMIZED CASE-CONTROLLED TRIAL ASSESSING MIDODRINE (GUTRON®) IN POSTOPERATIVE VASOPLEGIC PATIENTS [NCT04440085]Phase 450 participants (Anticipated)Interventional2020-09-14Not yet recruiting
Midodrine is Effective in Management of Intradialytic Hypotension Among Critically-ill Patients With Acute Kidney Injury [NCT03431194]80 participants (Actual)Interventional2016-10-01Completed
A Multi-Center, Double-Blind, Randomized, Placebo-controlled, Crossover Study to Assess the Clinical Benefit of Midodrine Hydrochloride in Subjects With Moderate to Severe Neurogenic Orthostatic Hypotension [NCT00555880]Phase 424 participants (Actual)Interventional2004-09-08Completed
Core Temperature During Cold Exposure in Persons With Tetraplegia [NCT01822535]Phase 430 participants (Actual)Interventional2011-07-31Completed
Efficacy and Safety of Midodrine and Atomoxetine Treatment in Patients With Neurogenic Orthostatic Hypotension : A Prospective Randomized Study [NCT03350659]Phase 450 participants (Actual)Interventional2018-01-01Completed
Blood Pressure, Cerebral Blood Flow and Cognition in SCI [NCT02307565]Phase 360 participants (Actual)Interventional2014-03-31Completed
Nor-epinephrine Versus Midodrine/Octreotide in Patients With Hepatorenal Acute Kidney Injury [NCT04522297]91 participants (Actual)Interventional2018-04-15Completed
To Study Effect of the Combination of Midodrine and Tolvaptan Versus Tolvaptan Alone in Patients With Severe Hyponatremia in Cirrhosis(TOLMINA Trial) - An Open Label Placebo Randomized Control Trial [NCT05060523]220 participants (Anticipated)Interventional2021-09-19Recruiting
A Phase 4, Randomized, Double-blind, Placebo-controlled, Crossover Study to Investigate the Clinical Benefit of Midodrine Hydrochloride in Male and Female Subjects With Symptomatic Orthostatic Hypotension [NCT01518946]Phase 424 participants (Actual)Interventional2012-05-14Completed
Treatment and Prognosis of Neurogenic Orthostatic Hypotension : A Prospective Randomized Study [NCT02308124]Phase 487 participants (Actual)Interventional2014-11-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00046475 (16) [back to overview]Percent of Participants Scored as Improved on The Patient Version of The CGI-I Scale
NCT00046475 (16) [back to overview]Change From Baseline in Short Form-36 (SF-36) Version 2 Health Survey Questionnaire Scores
NCT00046475 (16) [back to overview]Change From Baseline in Standing Blood Pressure (BP)
NCT00046475 (16) [back to overview]Change From Baseline in Supine BP
NCT00046475 (16) [back to overview]Change From Baseline in The OHSA Items 2 Through 6 Scores
NCT00046475 (16) [back to overview]Change From Baseline in The Orthostatic Hypotension Daily Activity Scale (OHDAS) Items 1 Through 4 Scores
NCT00046475 (16) [back to overview]Convergent Validity of the Intent-to-Treat (ITT) Population
NCT00046475 (16) [back to overview]Responsiveness of the Intent-to-Treat (ITT) Population
NCT00046475 (16) [back to overview]Change From Baseline in The OHSA Composite Symptom Score
NCT00046475 (16) [back to overview]Change From Baseline in The Orthostatic Hypotension Global Daily Activity Score
NCT00046475 (16) [back to overview]Percent of Participants Scored as Improved on The Clinician Version of The Clinical Global Impressions Improvement (CGI-I) Scale
NCT00046475 (16) [back to overview]Test Reliability of the Intent-to-Treat (ITT) Population
NCT00046475 (16) [back to overview]Post-treatment OHSA Item 1 Score of United States (US) Participants With Mild/Moderate Disease According to The Clinical Global Impressions-Severity (CGI-S) Scale
NCT00046475 (16) [back to overview]Post-treatment OHSA Item 1 Score of US Participants With Marked/Severe Disease According to The CGI-S Scale
NCT00046475 (16) [back to overview]Post-treatment Score For Item 1 of The Orthostatic Hypotension Symptom Assessment (OHSA) Scale
NCT00046475 (16) [back to overview]Re-analysis of The Post-treatment Score For Item 1 of The OHSA Scale, Excluding Two Sites
NCT00108355 (2) [back to overview]Time to Recurrence of Ascites.
NCT00108355 (2) [back to overview]Development of Post-paracentesis Circulatory Dysfunction (PCD)
NCT00426842 (1) [back to overview]Systolic Blood Pressure
NCT00555880 (18) [back to overview]Final Blood Pressure During Tilt Table Testing
NCT00555880 (18) [back to overview]Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
NCT00555880 (18) [back to overview]Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test
NCT00555880 (18) [back to overview]Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test
NCT00555880 (18) [back to overview]Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
NCT00555880 (18) [back to overview]Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
NCT00555880 (18) [back to overview]Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
NCT00555880 (18) [back to overview]Scores for 6 Items of The OHSA
NCT00555880 (18) [back to overview]Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
NCT00555880 (18) [back to overview]Duration of The Effect of Treatment at 3 Hours Post-dose
NCT00555880 (18) [back to overview]Time to Near-syncopal Symptoms at Treatment Visit 1
NCT00555880 (18) [back to overview]Time to Onset of Near-syncopal Symptoms During Tilt Table Testing
NCT00555880 (18) [back to overview]Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2
NCT00555880 (18) [back to overview]Time to Onset of Near-syncopal Symptoms During Tilt Table Testing-Re-analysis With The Koch Procedure
NCT00555880 (18) [back to overview]Time to Onset of Near-syncopal Symptoms in The Per-protocol Population
NCT00555880 (18) [back to overview]Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2
NCT00555880 (18) [back to overview]Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA)
NCT00555880 (18) [back to overview]Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
NCT00835224 (1) [back to overview]Blood Pressure
NCT01515865 (1) [back to overview]Percent of Subjects Who Failed to Maintain a Response
NCT01518946 (1) [back to overview]Time to Onset of Syncope/Near Syncope While on Tilt Table
NCT01531959 (5) [back to overview]Hospital Length of Stay
NCT01531959 (5) [back to overview]Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias
NCT01531959 (5) [back to overview]Rates of ICU Readmission
NCT01531959 (5) [back to overview]Time Until Discontinuation of IV Vasopressors
NCT01531959 (5) [back to overview]ICU Length of Stay
NCT01822535 (4) [back to overview]Visit 1: Percent Change in Core Body Temperature
NCT01822535 (4) [back to overview]Visit 1: Percent Changes in Cognitive Performance - Delayed Recall
NCT01822535 (4) [back to overview]Visit 1: Percent Changes in Cognitive Performance - Stroop Interference
NCT01822535 (4) [back to overview]Visit 2: Percent Change in Core Body Temperature With Midodrine
NCT02154243 (2) [back to overview]Change in Orthostatic Hypotension Questionnaire Score
NCT02154243 (2) [back to overview]Length of Stay
NCT02308124 (5) [back to overview]Change of the Depression Score (Beck Depression Inventory-II )
NCT02308124 (5) [back to overview]Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)).
NCT02308124 (5) [back to overview]Changes in Health-related Quality of Life
NCT02308124 (5) [back to overview]Short-form 36 Version 2
NCT02308124 (5) [back to overview]Change in Orthostatic BP Drop

Percent of Participants Scored as Improved on The Patient Version of The CGI-I Scale

"The CGI-I is a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Clinical Global Impressions ratings are completed with respect to neurogenic OH symptoms. A value of 0 was used if the investigator or patient assessment was not performed. The improved category is made up of patients who were evaluated as very much improved, much improved, or slightly improved for the classification of Overall Improvement. The CGI-I was completed at Visit 5 (Period 2) and Visit 6 (study completion)." (NCT00046475)
Timeframe: From the time of titration until the end of treatment

Interventionpercent of participants (Number)
Midodrine HCl62.5
Placebo50.0

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Change From Baseline in Short Form-36 (SF-36) Version 2 Health Survey Questionnaire Scores

"The SF-36 consists of 36 items in eight domains: physical functioning, general health, role-physical, bodily pain, vitality, social functioning, role-emotional, and mental health. Version 2 references one week ago for some questions. Raw scale scores for the SF-36 were transformed to a 0-100 scale with a higher score indicating a better quality of life. A positive change from baseline indicates that symptoms have improved. The SF-36 was completed at Visit 5 (Period 2) and Visit 6 (study completion) and compared to the score from Visit 3A (titration)." (NCT00046475)
Timeframe: From the time of titration until the end of treatment

,
Interventionscores on a scale (Mean)
General HealthPhysical Functioning
Midodrine HCl1.971.99
Placebo1.591.71

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Change From Baseline in Standing Blood Pressure (BP)

Standing BP was measured at Visit 5 (Period 2) and Visit 6 (study completion) and compared to measurements taken at Visit 3A (titration). Standing BP was measured 3 minutes after the patient rose from the supine position or as soon as the patient indicated they needed to sit down. If the patient indicated he or she needed to sit down, the BP measurement was taken while in the standing position, before the patient sat down. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

,
InterventionmmHg (Mean)
Systolic PressureDiastolic Pressure
Midodrine HCl10.75.9
Placebo2.81.5

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Change From Baseline in Supine BP

Supine BP was measured at Visit 5 (Period 2) and Visit 6 (study completion) and compared to measurements taken at Visit 3A (titration). Supine BP was measured after the patient had been in the supine position for 5 minutes. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

,
InterventionmmHg (Mean)
Systolic PressureDiastolic Pressure
Midodrine HCl7.63.4
Placebo-0.90.3

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Change From Baseline in The OHSA Items 2 Through 6 Scores

Items 2 through 6 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of the following symptoms whenever he or she was standing and that improved when he or she sat down or laid down: Item 2 addresses problems with vision (blurring, seeing spots, tunnel vision, etc); Item 3, weakness; Item 4, fatigue; Item 5, trouble concentrating; and Item 6, head or neck discomfort. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

,
Interventionscores on a scale (Mean)
Item 2, n= 103, 103Item 3, n=103, 103Item 4, n=103, 103Item 5, n=102, 102Item 6, n=102, 102
Midodrine HCl-1.2-1.3-1.2-0.4-0.8
Placebo-0.2-0.4-0.40.0-0.5

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Change From Baseline in The Orthostatic Hypotension Daily Activity Scale (OHDAS) Items 1 Through 4 Scores

The OHDAS had 4 items that asked the patient to give a graduated score from 0 (no limitation due to OH) to 10 (complete limitation due to OH). Item 1 addressed activities that required standing for a short time; Item 2, activities that required standing for a long time; Item 3, activities that required walking for a short time; and Item 4, activities that required walking for a long time. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

,
Interventionscores on a scale (Mean)
Item 1, n=102, 101Item 2, n=98, 99Item 3, n=100, 101Item 4, n=89, 90
Midodrine HCl-1.1-1.8-1.1-1.3
Placebo-0.4-0.6-0.2-0.5

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Convergent Validity of the Intent-to-Treat (ITT) Population

Item 1 of the OHSA and the OHSA composite score were analyzed for convergent validity with the CGI-I-Clinician scores. The change from baseline in the CGI-I scores are correlated with the OHSA Item 1 score change from baseline and the OHSA composite score change from baseline for the subjects in the ITT population. Values shown are Spearman correlation coefficients. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

Interventioncorrelation coefficient (Number)
OHSA Item 1, n=103OHSA Composite Score, n=102
ITT Population0.360.38

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Responsiveness of the Intent-to-Treat (ITT) Population

Item 1 of the OHSA, the OHSA composite score, and the OHDAS global daily activity score were analyzed for responsiveness as a measure of validity. Assuming that subjects who received Placebo during Randomization Period 1 are stable between Visit 3A and Visit 5, and using them as the stable subjects, responsiveness was calculated as [(OH CFB in Midodrine group)-(OH CFB in Placebo group)]/(SD of OH CFB in Placebo group), where CFB is change from baseline, SD is the standard deviation of OH CFB of the stable subjects; the value reported is the quotient of this equation. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

Interventionquotient (Number)
OHSA Item 1OHSA Composite ScoreOHDAS Global Daily Activity Score
ITT Population-0.4099-0.4014-0.4903

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Change From Baseline in The OHSA Composite Symptom Score

The OHSA composite symptom score was calculated by taking the average of the ratings for the symptoms present at Baseline. Participants were asked to rate symptoms by using a 0-10 scale (0 meaning not bothered and 10 meaning the worst). For subsequent visits, only those symptoms present at Baseline were scored. In this manner, a score was produced that represents the severity (and subsequent change in severity) of the patient's neurogenic OH symptoms, regardless of how many symptoms are presented at Baseline. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

Interventionscores on a scale (Mean)
Midodrine HCl-1.3
Placebo-0.54

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Change From Baseline in The Orthostatic Hypotension Global Daily Activity Score

The OHDAS global daily activity score was calculated as the average of all daily activity item scores. The OHDAS had 4 items that asked the patient to give a graduated score from 0 (no limitation due to OH) to 10 (complete limitation due to OH) to activities that required standing for a short time, standing for a long time, walking for a short time, walking for a long time. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

Interventionscores on a scale (Mean)
Midodrine HCl-1.4
Placebo-0.4

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Percent of Participants Scored as Improved on The Clinician Version of The Clinical Global Impressions Improvement (CGI-I) Scale

"The CGI-I is a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Clinical Global Impressions ratings are completed with respect to neurogenic OH symptoms. A value of 0 was used if the investigator or patient assessment was not performed. The improved category is made up of patients who were evaluated as very much improved, much improved, or slightly improved for the classification of Overall Improvement. The CGI-I was completed at Visit 5 (Period 2) and Visit 6 (study completion)." (NCT00046475)
Timeframe: From the time of titration until the end of treatment

Interventionpercent of participants (Number)
Midodrine HCl73.1
Placebo45.2

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Test Reliability of the Intent-to-Treat (ITT) Population

Item 1 of the OHSA, the OHSA composite score, and the OHDAS global daily activity score were analyzed for test-retest reliability as a measure of validity. Test-retest reliability is the Pearson product-moment correlation coefficient calculated between OHQ scores at Visit 3A (baseline measure) and OHQ scores at Visit 5 for the subjects who received Placebo during Randomization Period 1. (NCT00046475)
Timeframe: From the time of titration until the end of treatment

Interventioncorrelation coefficient (Number)
OHSA Item 1OHSA Composite ScoreOHDAS Global Daily Activity Score
ITT Population0.530.610.66

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Post-treatment OHSA Item 1 Score of United States (US) Participants With Mild/Moderate Disease According to The Clinical Global Impressions-Severity (CGI-S) Scale

Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. The results are reported by degree of severity according to the CGI-S scale, which uses 4 categories to describe disease severity: Mild, Moderate, Marked, and Severe. The Item 1 scores reported are grouped for participants with Mild or Moderate disease severity. Higher scores indicate more severe disease. (NCT00046475)
Timeframe: End of 2-week treatment period

Interventionscores on a scale (Mean)
Midodrine HCl4.4
Placebo3.8

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Post-treatment OHSA Item 1 Score of US Participants With Marked/Severe Disease According to The CGI-S Scale

Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. The results are reported by degree of severity according to the CGI-S scale, which uses 4 categories to describe disease severity: Mild, Moderate, Marked, and Severe. The Item 1 scores reported are grouped for participants with Marked or Severe disease severity. Higher scores indicate more severe disease. (NCT00046475)
Timeframe: End of 2-week treatment period

Interventionscores on a scale (Mean)
Midodrine HCl4.7
Placebo6.1

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Post-treatment Score For Item 1 of The Orthostatic Hypotension Symptom Assessment (OHSA) Scale

Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. Higher scores indicate more severe disease. (NCT00046475)
Timeframe: End of 2-week treatment period

Interventionscores on a scale (Mean)
Midodrine HCl4.1
Placebo5.2

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Re-analysis of The Post-treatment Score For Item 1 of The OHSA Scale, Excluding Two Sites

Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. Higher scores indicate more severe disease. (NCT00046475)
Timeframe: End of 2-week treatment period

Interventionscores on a scale (Mean)
Midodrine HCl4.3
Placebo5.1

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Time to Recurrence of Ascites.

Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group) (NCT00108355)
Timeframe: Variable depending on the patient, average 10 days

Interventiondays (Median)
Albumin (Control Group)10
Vasoconstrictor (Treatment Group)8

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Development of Post-paracentesis Circulatory Dysfunction (PCD)

Defined as an increase in Plasma Renin Activity (PRA) by >50% from baseline to a level > 4 ng/mL/h at post-paracentesis day (NCT00108355)
Timeframe: 6 days after paracentesis

Interventionparticipants (Number)
Albumin (Control Group)2
Vasoconstrictor (Treatment Group)2

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Systolic Blood Pressure

brachial artery systolic blood pressure (mmHg) (NCT00426842)
Timeframe: The difference between the average supine systolic blood pressure and the average systolic blood pressure at 45 degree head-up tilt position.

,,
InterventionmmHg (Mean)
Baseline Blood PressureHead-up Tilt Blood Pressure
Midodrine 10 mg102109
Midodrine 5 mg9796
No-drug9887

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Final Blood Pressure During Tilt Table Testing

Blood pressure was recorded just before tilt table testing and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. (NCT00555880)
Timeframe: 1 hour post-dose

,
InterventionmmHg (Mean)
Systolic PressureDiastolic Pressure
Midodrine HCl106.570.6
Placebo90.260.6

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Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2

Heart rate was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. (NCT00555880)
Timeframe: 1 and 3 hours post-dose

,
Interventionbeats per minute (Mean)
At 1 minute 1 hour post-dose, n= 11, 13At 10 minutes 1 hour post-dose, n= 10, 8At 1 minute 3 hours post-dose, n= 11, 12At 10 minutes 3 hours post-dose, n= 8, 6
Midodrine HCl77.677.779.780.9
Placebo80.579.580.981.3

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Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test

"The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The clinician completed the CGI-I after each of the tilt table tests. A patient was assessed as Improved if the score was 1, 2, or 3. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out." (NCT00555880)
Timeframe: 1 and 3 hours post-dose

,
Interventionparticipants (Number)
Treatment Visit 1- 1 hour post-dose, n=13, 11Treatment Visit 2- 1 hour post-dose, n=11, 13Treatment Visit 2- 3 hour post-dose, n= 11, 12
Midodrine HCl463
Placebo445

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Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test

"The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The patient completed the CGI-I after each of the tilt table tests. A patient was assessed as Improved if the score was 1, 2, or 3. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out." (NCT00555880)
Timeframe: 1 and 3 hours post-dose

,
Interventionparticipants (Number)
Treatment Visit 1-1 hour post-dose, n= 13, 11Treatment Visit 2-1 hour post-dose, n= 11, 13Treatment Visit 2-3 hour post-dose, n= 11, 12
Midodrine HCl353
Placebo233

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Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge

For biochemistry, blood samples (10.0mL) were taken at screening, admission (if greater than 14 days since screening) and discharge/early termination. The following parameters were assessed: sodium, potassium, calcium, blood urea nitrogen (BUN)/Urea, creatinine, albumin, total protein and albumin/globulin (A/G) ratio, globulin, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, glucose, chloride, and creatine kinase. A shift in reference to normal was either lower or higher at discharge. (NCT00555880)
Timeframe: Baseline to discharge

Interventionparticipants (Number)
SodiumPotassiumCalciumBUN/UreaCreatinineAlbuminTotal protein and A/G ratioGlobulinALTASTALPGGTTotal bilirubinGlucoseChlorideCreatine kinase
All Participants0210102000101601

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Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge

For hematology, blood samples (5.0mL) were taken at screening, study admission (if greater than 14 days since screening) and discharge/early termination. The following parameters were assessed: hemoglobin, hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count - total and differential (WBC), and platelet count. A shift in reference to normal was either lower or higher at discharge. (NCT00555880)
Timeframe: Baseline to discharge

Interventionparticipants (Number)
HemoglobinHematocritRBCMCVMCHMCHCWBCPlatelet count
All Participants10000210

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Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge

For urinalysis, samples were taken at screening, study admission (if greater than 14 days since screening) and discharge/early termination): glucose, blood, protein, pH, specific gravity, leukocyte esterase, and microscopic examination. A shift in reference to normal was higher at discharge. (NCT00555880)
Timeframe: Baseline to discharge

Interventionparticipants (Number)
GlucoseBloodProteinpHSpecific gravityLeukocyte esteraseMicroscopic examination
All Participants1200020

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Scores for 6 Items of The OHSA

"The OHSA measures the severity of six symptoms/symptom complexes associated with OH: dizziness, lightheadedness, and feeling faint; problems with vision; weakness; fatigue; trouble concentrating; and head/neck discomfort. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from none to worst possible. Scores for each subscale range from 0 (no symptoms) to 10 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured with straps to prevent injury. After an equilibration period with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, and feeling faint." (NCT00555880)
Timeframe: Approximately 1 hour post-dose

,
Interventionscores on a scale (Mean)
Dizziness, Lightheadedness, and Feeling FaintProblems with VisionWeaknessFatigueTrouble ConcentratingHead/Neck Discomfort
Midodrine HCl3.41.53.02.71.71.9
Placebo4.72.74.13.52.62.1

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Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2

Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. (NCT00555880)
Timeframe: 1 and 3 hours post-dose

,
InterventionmmHg (Mean)
At 1 minute 1 hour post-dose, n= 11, 13At 1 minute 3 hours post-dose, n= 11, 12At 10 minutes 1 hour post-dose, n= 10, 8At 10 minutes 3 hours post-dose, n= 7, 6
Midodrine HCl142.2110.1121.7108.3
Placebo97.394.9102.9107.2

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Duration of The Effect of Treatment at 3 Hours Post-dose

Duration of effect was defined as the difference in time to onset of near-syncopal symptoms between the first and second tilt table test, conducted at 1 hour and 3 hours post-dose, respectively, at Treatment Visit 2 (time to onset at 3 hours minus time at 1 hour). The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. (NCT00555880)
Timeframe: 1 and 3 hours post-dose

Interventionseconds (Mean)
Midodrine HCl45.1
Placebo48.0

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Time to Near-syncopal Symptoms at Treatment Visit 1

The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. (NCT00555880)
Timeframe: 1 hour post-dose

Interventionseconds (Least Squares Mean)
Midodrine HCl539.5
Placebo448.4

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Time to Onset of Near-syncopal Symptoms During Tilt Table Testing

The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. (NCT00555880)
Timeframe: 1 hour post-dose

Interventionseconds (Mean)
Midodrine HCl551.3
Placebo461.0

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Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2

The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 1 but the summary data are presented as least squares mean (standard error). (NCT00555880)
Timeframe: 1 hour post-dose

Interventionseconds (Least Squares Mean)
Midodrine HCl552.4
Placebo460.0

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Time to Onset of Near-syncopal Symptoms During Tilt Table Testing-Re-analysis With The Koch Procedure

The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. The Koch procedure is a 3-step process to analyze results while utilizing the available information on magnitude of differences. (NCT00555880)
Timeframe: 1 hour post-dose

Interventionseconds (Mean)
Midodrine HCl551.3
Placebo461.0

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Time to Onset of Near-syncopal Symptoms in The Per-protocol Population

The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. (NCT00555880)
Timeframe: 1 hour post-dose

Interventionseconds (Mean)
Midodrine HCl544.3
Placebo447.9

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Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2

The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 4 but the summary data are presented as least squares mean (standard error). (NCT00555880)
Timeframe: 1 hour post-dose

Interventionseconds (Least Squares Mean)
Midodrine HCl545.1
Placebo447.2

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Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA)

"The OHSA measures the severity of six symptoms/symptom complexes associated with orthostatic hypotension. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from none to worst possible. The OHSA total score is the sum of six subscales, ranging from 0 (no symptoms) to 60 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out." (NCT00555880)
Timeframe: Approximately 1 hour post-dose

Interventionscores on a scale (Least Squares Mean)
Midodrine HCl13.7
Placebo19.4

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Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2

Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. (NCT00555880)
Timeframe: 1 and 3 hours post-dose

,
InterventionmmHg (Mean)
At 1 minute 1 hour post-dose, n= 11, 12At 10 minutes 1 hour post-dose, n= 10, 8At 1 minute 3 hours post-dose, n= 11, 12At 10 minutes 3 hours post-dose, n= 7, 6
Midodrine HCl81.579.666.169.3
Placebo60.864.960.360.7

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Blood Pressure

(NCT00835224)
Timeframe: Blood pressure during the 4 hour period after no drug, L-NAME (IV: 1.0 mg/kg) and midodrine (PO: 10.0 mg) administration

InterventionmmHg (Mean)
Arm 1A120
Arm 1B112
Arm 2A117
Arm 2B109
Arm 3A96
Arm 3B109

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Percent of Subjects Who Failed to Maintain a Response

Failure to maintain a response was defined as any randomized subject that met both criterion 1 and criterion 2 below on Day 16: 1. The Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 score increased by >=4 points compared to baseline. OHSA Item 1 is a dizziness scale that is scored on a range from 0 (no dizziness) to 10 (severe dizziness). A lower score indicates less severe symptoms. 2. There was an increase in the number of syncopal/near syncopal events or severity of events within 15 minutes of standing compared to those observed at baseline. Syncope was defined as a loss of consciousness, and near syncope was defined as a feeling (e.g., dizziness, lightheadedness, feeling faint, feeling as though one would black out) that, without intervention, would lead to a loss of consciousness. (NCT01515865)
Timeframe: 30 minutes post-dose on Day 16

Interventionpercentage of participants (Number)
Midodrine HCl30.3
Placebo44.1

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Time to Onset of Syncope/Near Syncope While on Tilt Table

After a 30-minute supine period, the table was tilted from 0-90º within 30 seconds and maintained in that position for 45 minutes or until endpoint. Subjects were monitored for near-syncopal symptoms (subject felt sufficiently dizzy, lightheaded, faint, or felt like they were about to black out and requested the table to be returned to horizontal). Such a report ended the test. Alternatively, if the investigator observed that the subject was about to lose consciousness, that also constituted an endpoint. (NCT01518946)
Timeframe: 1 hour post-dose

Interventionseconds (Least Squares Mean)
Placebo1105.6
Midodrine HCl1626.6

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Hospital Length of Stay

Measured number of days from initiation of midodrine until discharged from hospital (NCT01531959)
Timeframe: From initiation of midodrine until hospital discharge, assessed up to 90 days

Interventiondays (Median)
Midodrine11.0
Placebo14.0

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Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias

Measured rates of hypertension (increase in systolic blood pressure to values higher than those set by the primary team or greater than 160 mmg), bradycardia (decrease in heart rate to values lower than those set by the primary team or less than 40 BPM), hemodynamically significant tachyarrythmias (greater than 20 mmhg decrease in systolic blood pressure). (NCT01531959)
Timeframe: From initiation of the study drug until discontinuation of the study drug, an average of 59 hours.

InterventionParticipants (Count of Participants)
Midodrine12
Placebo3

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Rates of ICU Readmission

Number of patients initiated on midodrine that are readmitted back to ICU after being discharged to floor (NCT01531959)
Timeframe: Up to 2 months after ICU discharge

InterventionParticipants (Count of Participants)
Midodrine1
Placebo3

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Time Until Discontinuation of IV Vasopressors

Measured hours from initiation of midodrine until discontinuation of IV vasopressors (NCT01531959)
Timeframe: From initiation of the study drug until discontinuation of IV vasopressors, assessed up to 400 hours

Interventionhours (Median)
Midodrine23.5
Placebo22.5

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ICU Length of Stay

Measured number of days from initiation of midodrine until discharge ready from the ICU (NCT01531959)
Timeframe: From initiation of midodrine until ICU discharge, assessed up to 45 days

Interventiondays (Median)
Midodrine6.0
Placebo6.0

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Visit 1: Percent Change in Core Body Temperature

We will test the effects of cool temperature (64°F) exposure, of up to 120 minutes, on the ability to maintain a constant body temperature (e.g., core temperature of 98.6°F) in persons with tetraplegia through comparing the percent changes in core body temperatures between groups from baseline to after cool exposure. (NCT01822535)
Timeframe: Baseline, Up to 2 hours

InterventionPercent Change (Mean)
Tetraplegia-1.2
Able-bodied0.05

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Visit 1: Percent Changes in Cognitive Performance - Delayed Recall

Cognitive performance will be evaluated using the Delayed Recall obtained using the Memory section of the Montreal Cognitive Assessment (MoCA). We will measure the change in cognitive performance in persons with tetraplegia after exposure to a cool environment (64°F) of up to 120 min in the seated position. Note: Scores are based on individual performance. All subjects are asked to remember two lists of five words (one list during baseline, and one list during cool Challenge). Lower scores indicate poorer performance, and a positive percent change in indicates improved cognitive performance. (NCT01822535)
Timeframe: Baseline, Up to 2 hours

InterventionPercent Change (Mean)
Tetraplegia-55.2
Able-bodied (AB)6.4

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Visit 1: Percent Changes in Cognitive Performance - Stroop Interference

Cognitive performance will be evaluated using the Interference T-Scores obtained using the Stroop Color and Word Test. We will measure the change in cognitive performance in persons with tetraplegia after exposure to a cool environment (64°F) of up to 120 min in the seated position. Note: Interference T-Scores are derived from the difference between the raw Color-Word score and the projected Color-Word score (which is, in turn, based on the raw scores obtained in the Word and Color portions of the Test). Lower scores indicate poorer performance, and a positive percent change in T-scores indicates improved performance. (NCT01822535)
Timeframe: Baseline, Up to 2 hours

InterventionPercent Change (Mean)
Tetraplegia-3.9
Able-bodied5.4

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Visit 2: Percent Change in Core Body Temperature With Midodrine

We will test the effects of midodrine on the ability to maintain a constant body temperature (e.g., core temperature of 98.6°F) after exposure to cool temperatures (64°F) in persons with tetraplegia through comparing the percent changes in core body temperature during visit 1 to percent changes in core body temperature during visit 2. (NCT01822535)
Timeframe: Baseline, Baseline Post-midodrine, Up to 2 hours

InterventionPercent Change (Mean)
Tetraplegia-2.2

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Change in Orthostatic Hypotension Questionnaire Score

(NCT02154243)
Timeframe: From baseline assessment to post-intervention (30 min, 1 hr, 2 hrs, 3 hrs, 4 hrs)

Intervention ()
Midodrine0
Intravenous Fluid Bolus0
Control (no Intervention)0

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Length of Stay

(NCT02154243)
Timeframe: Length of the hospital stay (average of 4 days)

Intervention ()
Midodrine0
Intravenous Fluid Bolus0
Control (no Intervention)0

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Change of the Depression Score (Beck Depression Inventory-II )

"Change of the depression score after 3-month medical treatment compared to initial results.~21 multiple-choice questions, each of which can be scored from 0 to 3. Higher score represent higher degree of depression.~Score Normal; 0-13, Mild depression; 14-19, Moderate depression; 20-28, Severe depression; 29-63" (NCT02308124)
Timeframe: after 3-month medical treatment.

Interventionpoints (Mean)
Midodrine Only-6.8
Pyridostigmine Only-7.8
Midodrine + Pyridostigmine-3.5

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Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)).

"Change of the OH associated symptom survey result after 3-month medical treatment compared to initial results.~OHQ questionnaire has two components: the OH daily activity scale (OHDAS), which contains 4 items measuring the impact of OH on daily activities, and the OH symptom assessment (OHSA), which contains 6 items measuring the symptoms of OH (dizziness/light headedness, vision disturbance, weakness, fatigue, trouble concentrating, and head/neck discomfort).This questionnaire reflects the severity of OH-related symptoms on a 10-point scale, with 0 indicating the absence of a symptom and 10 indicating maximal severity.~** OHQ total score minimal 0 ~ maximal 100" (NCT02308124)
Timeframe: after 3-month medical treatment.

Interventionpoints (Mean)
Midodrine Only-16.2
Pyridostigmine Only-17.2
Midodrine + Pyridostigmine-12.6

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Short-form 36 Version 2

"changes in Short Form (36) Health Survey version 2 (SF-36v2) physical component summary scale (PCS) compared to the baseline~SF-36v2 measures eight HRQOL domains (physical functioning, role limitation caused by physical problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health) summarized into two summary scales that are normalized to the population (mean=50, standard deviation=10): the physical component summary scale (PCS) and the mental component summary scale (MCS).20 Better HRQOL is reflected by higher SF-36v2 scores." (NCT02308124)
Timeframe: changes at 3 months after treatment

Interventionpoints (Mean)
Midodrine Only5.6
Pyridostigmine Only4.2
Midodrine + Pyridostigmine2.7

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Change in Orthostatic BP Drop

Change of orthostatic SBP and DBP drop after 3-month medical treatment compared to initial results. (NCT02308124)
Timeframe: after 3-month medical treatment

,,
InterventionmmHg (Mean)
Changes in SBP dropChanges in DBP drop
Midodrine + Pyridostigmine8.97.4
Midodrine Only11.17.5
Pyridostigmine Only13.611.1

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