isosorbide profile

Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	12597
CHEMBL ID	1200660
CHEBI ID	6060
SCHEMBL ID	15495
MeSH ID	M0011786

Synonym
BIDD:GT0695
isosorbida
isosorbidum
wxr179l51s ,
ec 211-492-3
isosorbide [usan:usp:inn:ban:jan]
unii-wxr179l51s
5-19-03-00201 (beilstein handbook reference)
at-101 ,
hydronol
isobide
ismotic
d-glucitol,4:3,6-dianhydro-
d-sorbitol,4:3,6-dianhydro(furo[3,2-b]furan-3,6-diol, hexahydro-)
glucitol,4:3,6-dianhydro-, d-
nsc40725
(+)-d-isosorbide
1,6-dianhydrosorbitol
652-67-5
nsc-40725
vascardin dinitrate
sorbid
1,6-dianhydro-d-sorbitol
1,4-dianhydrosorbitol
isosorbide
1,6-dianhydro-d-glucitol
devicoran
SMP1_000177
dianhydro-d-glucitol
1,4:3,6-dianhydrosorbitol
d-1,4:3,6-dianhydroglucitol
brn 0080510
isosorbidum [inn-latin]
hsdb 3105
glucitol, 1,4:3,6-dianhydro-, d-
hydronol (van)
nsc 40725
isosorbida [inn-spanish]
einecs 211-492-3
1,4:3,6-dianhydro-d-glucitol
NCGC00160508-01
D00347
isobide (tn)
ismotic (tn)
isosorbide (jp17/usp/inn)
dianhydro-d-glucitol, 98%
1,4:3,6-dianhydro-d-sorbitol
(3s,3ar,6r,6ar)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diol
d-glucitol, 1,4:3,6-dianhydro-
d-sorbitol, {1,4:3,6-dianhydro(furo[3,2-b]furan-3,6-diol,} hexahydro-)
A912284D-27E1-4FB0-91B8-86C8AB905297
sorbitol, 1,4:3,6-dianhydro-
CHEMBL1200660
I0407
1,4:3,6-dianhydroglucitol
STK801813
AKOS005622709
NCGC00160508-02
dtxsid5046196 ,
dtxcid3026196
cas-652-67-5
tox21_111861
S4204
(3r,3ar,6s,6ar)-hexahydrofuro[3,2-b]furan-3,6-diol
isosorbide [jan]
isosorbide [inn]
isosorbide [who-dd]
isosorbide [usp impurity]
isosorbide [orange book]
isosorbide [hsdb]
isosorbide [mart.]
isosorbide [usp-rs]
isosorbide [usan]
isosorbide [vandf]
isosorbide [inci]
isosorbide [mi]
BBL029591
SCHEMBL15495
NCGC00160508-03
tox21_111861_1
d-isosorbide
HY-B1469
CS-5157
1.4;3.6-dianhydro-d-glucitol
1.4:3.6-dianhydro-d-glucitol
1,4; 3,6-dianhydrosorbitol
AB01566931_01
mfcd00064827
CHEBI:6060
d-isosorbide;dianhydro-d-glucitol
DB09401
AS-14140
Q1243800
CCG-266173
isosorbide 100 microg/ml in acetonitrile
EN300-170910
Z1216815730
28980-83-8
rel-(3r,3ar,6s,6ar)-hexahydrofuro[3,2-b]furan-3,6-diol
isosorbide (usan:usp:inn:ban:jan)
isosorbide (usp-rs)
isosorbidum (inn-latin)
isosorbide (usp impurity)
isosorbide (mart.)
isosorbida (inn-spanish)

Excerpt	Reference
"Isosorbide (ISO) is an effective hyperosmotic agent that can be administrated orally and is used as a therapeutic agent for brain pressure drop, glaucoma, and Meniere's disease. "	( Ito, M; Noguchi, S; Suzuki, H; Terada, K; Watanabe, T, 2021)
"Isosorbide is a promising biomass-derived molecule that can be used as a replacement for fossil resource-derived diol monomers used in polyester synthesis. "	( Im, SS; Lee, J; Lee, S; Moon, B; Oh, HB; Yoon, D; Yoon, WJ, 2013)
"Isosorbide is a non-toxic biodegradable diol derived from bio-based feedstock. "	( Battegazzore, D; Bocchini, S; Frache, A; Martini, E; Nicola, G, 2015)
"As isosorbide is a non-symmetric diol, the two hydroxyl groups display different reactivities."	( Aubry, JM; Bigot, S; Castanet, Y; Lai, J; Molinier, V; Mortreux, A; Sauthier, M; Suisse, I, 2011)
"Isosorbide is a platform chemical of considerable importance for the future replacement of fossil resource-based products. "	( Palkovits, R; Rose, M, 2012)

Class	Description
organic molecular entity	Any molecular entity that contains carbon.
[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]

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
GLI family zinc finger 3	Homo sapiens (human)	Potency	33.4915	0.0007	14.5928	83.7951	AID1259369
euchromatic histone-lysine N-methyltransferase 2	Homo sapiens (human)	Potency	3.5481	0.0355	20.9770	89.1251	AID504332
peripheral myelin protein 22	Rattus norvegicus (Norway rat)	Potency	16.1366	0.0056	12.3677	36.1254	AID624032
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Assay ID	Title	Year	Journal	Article
AID504749	qHTS profiling for inhibitors of Plasmodium falciparum proliferation	2011	Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043	Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1347089	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347425	Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)	2019	The Journal of biological chemistry, 11-15, Volume: 294, Issue:46	Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347106	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID651635	Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1347094	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347086	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347100	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154	Primary screen GU AMC qHTS for Zika virus inhibitors	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347090	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347083	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347103	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1296008	Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening	2020	SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1	Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347107	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1745845	Primary qHTS for Inhibitors of ATXN expression
AID1347092	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347082	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347424	RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)	2019	The Journal of biological chemistry, 11-15, Volume: 294, Issue:46	Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1508630	Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay	2021	Cell reports, 04-27, Volume: 35, Issue:4	A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347108	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347104	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1346987	P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID728847	Antiplatelet aggregation activity in rabbit platelets assessed as inhibition of ADP-induced platelet aggregation at 1 mM incubated for 5 mins prior to ADP-challenge measured within 5 mins by Born's turbidimetric analysis relative to control	2013	Journal of medicinal chemistry, Apr-11, Volume: 56, Issue:7	Novel hybrids of optically active ring-opened 3-n-butylphthalide derivative and isosorbide as potential anti-ischemic stroke agents.
AID625277	FDA Liver Toxicity Knowledge Base Benchmark Dataset (LTKB-BD) drugs of less concern for DILI	2011	Drug discovery today, Aug, Volume: 16, Issue:15-16	FDA-approved drug labeling for the study of drug-induced liver injury.
AID728848	Antiplatelet aggregation activity in rabbit platelets assessed as inhibition of arachidonic acid-induced platelet aggregation incubated for 5 mins prior to arachidonic acid-challenge measured within 5 mins by Born's turbidimetric analysis	2013	Journal of medicinal chemistry, Apr-11, Volume: 56, Issue:7	Novel hybrids of optically active ring-opened 3-n-butylphthalide derivative and isosorbide as potential anti-ischemic stroke agents.
AID728849	Antiplatelet aggregation activity in rabbit platelets assessed as inhibition of ADP-induced platelet aggregation incubated for 5 mins prior to ADP-challenge measured within 5 mins by Born's turbidimetric analysis	2013	Journal of medicinal chemistry, Apr-11, Volume: 56, Issue:7	Novel hybrids of optically active ring-opened 3-n-butylphthalide derivative and isosorbide as potential anti-ischemic stroke agents.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	71 (27.41)	18.7374
1990's	34 (13.13)	18.2507
2000's	48 (18.53)	29.6817
2010's	80 (30.89)	24.3611
2020's	26 (10.04)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	33 (12.22%)	5.53%
Reviews	14 (5.19%)	6.00%
Case Studies	25 (9.26%)	4.05%
Observational	0 (0.00%)	0.25%
Other	198 (73.33%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (69)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
Nitrate Effect on Exercise Capacitance and Hemodynamic Profile Prior to Fontan Failure[NCT04297241]	Phase 2	20 participants (Actual)	Interventional	2019-12-12	Completed
Effect of Nicorandil, Diltiazem or Isosorbide Mononitrate for Oral Antispastic Therapy After Coronary Artery Bypass Grafting Using Radial Artery Grafts - A Pilot Randomized Controlled Trial[NCT04310995]	Phase 4	150 participants (Actual)	Interventional	2020-06-02	Completed
The Effect of Sumatriptan and Placebo on Isosorbide-5-mononitrate Induced Headache. Development of a Pragmatic Migraine Model[NCT02485340]		30 participants (Actual)	Interventional	2015-04-30	Completed
Nitric Oxide Donor Isosorbide Mono Nitrate for Cervical Ripening in Induction of Labor in Term or Post Term Pregnancies in Females With Pre-labor Rupture of Membranes[NCT03665779]	Phase 3	140 participants (Actual)	Interventional	2018-08-01	Completed
A Randomized, Open Label, Balanced, Single Dose, 3-way Crossover Bioequivalence Study of Two Isosorbide -5 -Mononitrate Extended -Release Tablets 40 mg and ISMO Retard 40 mg Under Fed Conditions in Healthy Subjects[NCT03557580]	Phase 1	12 participants (Actual)	Interventional	2018-04-17	Completed
A Randomized, Open-label, One Dose, 2-way Crossover Study to Evaluate the Bioequivalence of Elantan SR* 60 mg in Comparison With Imdur SR* 60 mg Under Fasted and Fed Conditions in Healthy Korean Male Subjects (*Sustained Release)[NCT02101710]	Phase 1	60 participants (Actual)	Interventional	2011-06-30	Completed
Intravaginal Isosorbide Mononitrate in Addition to Misoprostol Versus Misoprostol Only for Induction of Labor: A Randomized Controlled Trial[NCT03523754]	Phase 1/Phase 2	50 participants (Anticipated)	Interventional	2018-01-01	Active, not recruiting
Study of Curative Effect Evaluation of DanLou Tablet on Coronary Artery Disease Not Amenable to Revascularization on the Basis of Western Medicine Therapy[NCT03072082]	Phase 4	440 participants (Anticipated)	Interventional	2017-06-30	Not yet recruiting
Nitric Oxide Donor Isosorbide Mono Nitrate for Cervical Ripening in Induction of Labor[NCT03544606]	Phase 3	140 participants (Actual)	Interventional	2019-01-01	Completed
Multi-center, Randomized, Placebo-controlled, Double-blind Group Comparison Study to Investigate Safety, Tolerability and Blood Pressure of 2.5 mg, 5.0 mg and 10 mg Vericiguat Each Given Over 14 ± 3 Days Together With Isosorbite Mononitrate (ISMN) 60 mg E[NCT03255512]	Phase 1	41 participants (Actual)	Interventional	2017-08-17	Completed
Prevention and Comparison of Different Forms of Administration of Nitrates in the Risk of Radial Spasm During Coronary Angiography.[NCT02258620]		442 participants (Actual)	Interventional	2013-06-30	Completed
A Four-arm, Single Dose, Two-Period, Pharmacokinetic Study of BiDil SR and IR Capsules and Commercial BiDil Tablets[NCT01587313]	Phase 1	36 participants (Actual)	Interventional	2012-04-30	Completed
Efficacy of Intravaginal Administration of Isosorbide Mononitrate Together With Misoprostol Versus Misoprostol Alone in Induction of Labor in Postdate Women[NCT03854383]	Phase 2	100 participants (Anticipated)	Interventional	2019-03-03	Recruiting
Randomized Controlled Trial of Nitric-oxide Donor (NOD) Isosorbide Mononitrate (IMN) Versus Placebo for Induction of Labor in Pregnancies Complicated by Preeclampsia[NCT03171480]	Phase 4	176 participants (Actual)	Interventional	2017-10-30	Completed
Medical Management of Late Intrauterine Death Using a Therapeutic Combination of Isosorbide Dinitrate and Oxytocin.[NCT02488642]	Phase 4	60 participants (Actual)	Interventional	2008-05-31	Completed
Ocular Hemodynamic Effects of Nitrovasodilators in Healthy Subjects[NCT00810381]		14 participants (Actual)	Interventional	1999-01-31	Completed
Renin-Angiotensin Aldosterone System and Fibrinolysis(RAAS) Interaction in Humans- Specific Aim 3[NCT00685945]		24 participants (Actual)	Interventional	2007-12-31	Completed
Effect of Adding Vaginal Isosorbide Mononitrate to Misoprostol Prior to Intrauterine Device Insertion in Women Delivered Only by Elective Cesarean Section: a Randomized Double-blind Controlled Clinical Trial[NCT03587077]		113 participants (Anticipated)	Interventional	2018-09-30	Not yet recruiting
The Effect of Isosorbide Diesters Based Moisturizer on Skin Health[NCT04831892]		34 participants (Actual)	Interventional	2021-04-12	Completed
Open Monocentric Clinical Study for the Evaluation of Efficacy and Safety of 20 mg Monocordil Tablets Manufactured by Laboratórios Baldacci in Patients With Stable Angina[NCT02152579]	Phase 3	86 participants (Anticipated)	Interventional	2014-07-31	Not yet recruiting
Vasodilation or Loop-diuretics for Initial Treatment of Pulmonary Edema or Congestion Due to Acute Heart Failure - a Randomized Placebo-controlled Trial[NCT05276219]	Phase 4	1,104 participants (Anticipated)	Interventional	2023-09-14	Recruiting
Misoprostol Plus Isosorbide Mononitrate Versus Misoprostol For Termination Of Anembryonic Pregnancy[NCT02573051]	Phase 2	108 participants (Anticipated)	Interventional	2015-06-30	Recruiting
Endoscopic Variceal Ligation Plus Propranolol And Isosorbide Mononitrate Versus Endoscopic Variceal Ligation Alone For Secondary Prophylaxis Of Variceal Bleeding: A Randomized Controlled Trial[NCT00766805]		177 participants (Actual)	Interventional	2002-10-31	Completed
Safety and Efficacy of the Effect of Isosorbide Mononitrate in Reducing Pain During Levonorgestrel-releasing Intrauterine Device Insertion in Adolescents and Young Women[NCT04311658]	Phase 3	88 participants (Anticipated)	Interventional	2020-03-30	Not yet recruiting
Uterine Artery Doppler Changes After Vaginal Administration of Isosorbide Mononitrate In Patients With Unexplained Recurrent Pregnancy Loss[NCT05341856]	Early Phase 1	60 participants (Anticipated)	Interventional	2022-05-01	Not yet recruiting
Misoprostol Versus Effox (Individually or in Combination) as Cervical Ripening Agent Prior to 1st Trimesteric Surgical Evacuation[NCT02738177]	Phase 2	90 participants (Anticipated)	Interventional	2015-11-30	Recruiting
A Randomized, Double-blind, Placebo Controlled Study (DANHEART): Hydralazine-ISDN in Patients With Chronic Heart Failure - Hydralazine Heart Failure Trial (H-HeFT) and Metformin in Patients With Chronic Heart Failure and Diabetes or Insulin Resistance - M[NCT03514108]	Phase 4	1,500 participants (Anticipated)	Interventional	2018-03-01	Recruiting
Treatment of Orthostatic Intolerance[NCT00262470]	Phase 1/Phase 2	150 participants (Anticipated)	Interventional	1997-04-30	Active, not recruiting
Nitric Oxide Donors for Treatment of Isolated Oligohydramnios: A Pilot Study[NCT02712125]	Phase 2/Phase 3	100 participants (Actual)	Interventional	2013-08-31	Completed
A Randomized, Double-Blind, Placebo-Controlled, 2-Part Study to Evaluate the Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis in Obese Patients With Hypertension[NCT00871871]	Phase 1	64 participants (Actual)	Interventional	2009-03-31	Completed
A Safety and Efficacy Study of Blood Pressure Control in Acute Heart Failure - A Pilot Study (PRONTO)[NCT00803634]	Phase 3	117 participants (Actual)	Interventional	2008-12-31	Completed
A Prospective, Placebo-controlled, Double-blind, Randomized Study to Compare Hydralazine-isosorbide-dinitrate(HYIS) Versus Placebo on Top of Std Care in African Patients With Acute Heart Failure (AHF) and Left Ventricular Dysfunction[NCT01822808]	Phase 3	500 participants (Anticipated)	Interventional	2013-01-31	Active, not recruiting
Effect of Organic Nitrates and Hydralazine on Wave Reflections and Left Ventricular Structure and Function in Heart Failure With Preserved Ejection Fraction[NCT01516346]	Phase 2	44 participants (Actual)	Interventional	2012-01-31	Completed
Effect of Pioglitazone on Insulin Resistance, Progression of Atherosclerosis and Clinical Course of Coronary Heart Disease[NCT03011775]	Phase 4	43 participants (Actual)	Interventional	2012-11-30	Completed
Secondary Prophylaxis After Variceal Bleeding: Combined Treatment With Endoscopic Ligation and Nadolol Against Nadolol Associated With Mononitrate of Isosorbide or Prazosin According to Hemodynamic Response.[NCT00450164]	Phase 4	50 participants	Interventional	2000-11-30	Completed
[NCT00000478]	Phase 3	0 participants	Interventional	1990-11-30	Completed
Phase I Clinical Trial to Evaluate the Pharmacokinetic Profile of a Formulation With Isosorbide Mononitrate 0.5% Gel - Manufactured by Sanus Pharmaceutical Ltda, to Intra Anal Application in Healthy Males and Females' Subjects[NCT04729088]	Phase 1	0 participants (Actual)	Interventional	2020-12-20	Withdrawn(stopped due to The sponsor will no longer develop the experimental drug.)
Targeting Wave Reflections to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function in Hypertension[NCT01961453]	Phase 2	0 participants (Actual)	Interventional	2013-08-31	Withdrawn(stopped due to Funding)
Comparison of Short-term Efficacy of Furosemide, Isosorbide Dinitrate and Their Combination in Patients With Acute Decompensated Heart Failure: A Randomized Controlled Trial[NCT02649998]		0 participants (Actual)	Interventional	2017-01-31	Withdrawn(stopped due to Lack of funding)
Influence of Nitrates on Bone Remodeling and Endothelial Function in Patients With Type 2 Diabetes Mellitus.[NCT02011620]	Phase 4	0 participants (Actual)	Interventional	2014-10-31	Withdrawn(stopped due to The sponsor was no longer in a position to sponsor a CTIMP. Study did not open.)
the Effect of Vaginal Isosorbide Mononitrate Administration in Reducing Pain During Cooper Intrauterine Device Insertion in Nulliparous Women : a Randomized Controlled Trial[NCT04312048]	Phase 3	110 participants (Actual)	Interventional	2020-04-15	Completed
Pain Perception, Headache Provocation and Multiomics of People Who Are Unable to Have Headache[NCT04217668]		58 participants (Actual)	Interventional	2019-12-02	Completed
Chinese People's Liberation Army General Hospital[NCT02718521]		400 participants (Anticipated)	Interventional	2016-03-31	Active, not recruiting
Pharmacokinetics, Pharmacodynamics and Safety Comparative Trial of Isosorbide Mononitrate Gel in Participants With Anal Fissure and Healthy Volunteers.[NCT02667535]	Phase 1	0 participants (Actual)	Interventional	2017-07-31	Withdrawn(stopped due to Study has been cancelled and it has not been initiated.)
Pain Perception, Headache Provocation and Multiomics of People Who Are Unable to Have Headache[NCT04218760]		58 participants (Actual)	Interventional	2019-10-10	Completed
Efficacy and Safety of Chinese Herbal Medicine Wen Xin Granules for the Treatment of Unstable Angina Pectoris With Yang Deficiency and Blood Stasis Syndrome: Study Protocol for a Randomized Controlled Trial[NCT04661709]	Phase 4	502 participants (Anticipated)	Interventional	2021-03-01	Not yet recruiting
A Double-Blind, Randomized, Placebo-Controlled, 5-Period Crossover Study to Evaluate the Effects of a Single Dose of Losartan, a Single Dose of Isosorbide Mononitrate (ISMN), and Single Doses of Losartan + ISMN on Central Blood Pressure Measurements in Mi[NCT00943852]	Phase 1	13 participants (Actual)	Interventional	2006-08-31	Completed
An Open Label, Randomized, Two Treatment, Two Sequence, Two Period, Cross-over, Single-dose Comparative Oral Bioavailability Study of Isosorbide Mononitrate 120 mg ER Tablets (Test) of Torrent Pharmaceuticals Ltd., India and Isosorbide Mononitrate 120 mg [NCT01418534]	Phase 1	0 participants	Interventional		Completed
An Open Label, Randomized, Two Treatment, Two Sequence, Two Period, Cross-over, Single-dose Comparative Oral Bioavailability Study of Isosorbide Mononitrate 120 mg ER Tablets (Test) of Torrent Pharmaceuticals Ltd., India and Isosorbide Mononitrate 120 mg [NCT01418547]	Phase 1	0 participants	Interventional		Completed
Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction[NCT02053493]	Phase 2	110 participants (Actual)	Interventional	2014-04-30	Completed
LACunar Intervention (LACI-2) Trial-2: Assessment of Safety and Efficacy of Cilostazol and Isosorbide Mononitrate to Prevent Recurrent Lacunar Stroke and Progression of Cerebral Small Vessel Disease.[NCT03451591]	Phase 2/Phase 3	363 participants (Actual)	Interventional	2018-01-08	Completed
Open, Randomized, 3 Period Cross-over Design, in Healthy Volunteers to Compare the Pharmacokinetics Profiles of 3 Treatments: ISO 20, IBU 200 and IBU Plus ISO Combinations (200 + 20) Administered Per os as Single Doses[NCT01478022]	Phase 1	12 participants (Actual)	Interventional	2011-10-31	Completed
A Randomized Double-blind Placebo-controlled Clinical Trials of the Blood-quickening Stasis-transforming Formula Quick-Acting Heart Reliever for Patients With Moderate Coronary Stenosis[NCT01513070]	Phase 4	120 participants (Anticipated)	Interventional	2012-04-30	Completed
Efficacy of the Combination of Isosorbide Dinitrate Spray and Chitosan in Diabetic Foot Ulcers[NCT02789033]	Phase 3	68 participants (Actual)	Interventional	2015-06-30	Completed
Randomized Clinical Trial of Cervical Ripening and Labor Induction Using Stepwise Oral Misoprostol With or Without Intravaginal Isosorbide Mononitrate[NCT00374621]		156 participants (Actual)	Interventional	2006-09-30	Completed
Non-inferiority Trial Comparing Pharmacological Prevention Alone Versus Pancreatic Stents Plus Pharmacological Prevention to Prevent Post-ERCP Pancreatitis[NCT02368795]		400 participants (Anticipated)	Interventional	2015-02-28	Recruiting
Isosorbide Mononitrate For Anti-Vascular Endothelial Growth Factor (VEGF) Induced Kidney Injury[NCT04051957]	Phase 2	9 participants (Actual)	Interventional	2019-09-26	Terminated(stopped due to Delays due to COVID and loss of research coordinator.)
Estimation of the Long Term Effectiveness of Routine Use of Cardiac Shock Wave Therapy in the General System of Noninvasive, Invasive, and Surgical Treatment of Ischemic Heart Disease in the Conditions of a Large General City Hospital[NCT01631409]		0 participants (Actual)	Observational	2013-09-30	Withdrawn(stopped due to The study has been withdrawn due to organizational problems)
Withdrawal of Nitrate in Patients With Stable Angina - Multicenter Clinical Trial[NCT01769079]	Phase 4	95 participants (Actual)	Interventional	2009-09-30	Completed
The Effect of Oral Isosorbide Mononitrate Therapy on Umbilical Artery Doppler Resistance Index in Pregnancies With Intrauterine Growth Restriction: Prospective Randomized Control Trial[NCT05800938]	Phase 4	46 participants (Actual)	Interventional	2022-06-08	Completed
One-year Outcome of Intensive Versus Standard Blood Pressure Treatment in Non-ST Elevation Acute Coronary Syndrome: A Randomised Controlled Trial[NCT02135315]		1,500 participants (Actual)	Interventional	2014-03-31	Completed
Randomized, Open-Label, Daily Dose, 2-sequence, 2-way Crossover Pharmacodynamic and Pharmacokinetic Study of BiDil XR Capsules and Commercial BiDil Tablets in Self-identified Black Patients, Who Are Slow Acetylators, With Heart Failure[NCT02522208]	Phase 1	12 participants (Actual)	Interventional	2015-09-30	Completed
Prospective Randomized Vehicle-Controlled, Double-Blind Assessment of the Effect of Coconut and Sunflower Seed Oil Derived Isosorbide Diseters and Colloidial Oatmeal[NCT05688735]		40 participants (Anticipated)	Interventional	2023-04-20	Recruiting
Preventing Cognitive Decline and Dementia From Cerebral Small Vessel Disease[NCT02481323]	Phase 2	57 participants (Actual)	Interventional	2016-03-31	Completed
Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate to Prevent Post-ERCP Pancreatitis: a Multicentre, Non-inferiority, Double-blind, Randomised Trial[NCT04425993]		2,700 participants (Actual)	Interventional	2020-07-01	Active, not recruiting
Isosorbide Mononitrate and Misoprostol in Induction of Labour[NCT04482881]	Early Phase 1	130 participants (Anticipated)	Interventional	2020-07-21	Not yet recruiting
Study of Curative Effect Evaluation of Shexiang Baoxin Pill on Coronary Artery Disease Not Amenable to Revascularization on the Basis of Western Medicine Therapy[NCT03072121]	Phase 4	440 participants (Anticipated)	Interventional	2017-06-30	Not yet recruiting
Nitrates In Combination With Hydralazine in cardiorEnal Syndrome (NICHE) Study[NCT02343393]	Phase 3	100 participants (Anticipated)	Interventional	2015-01-31	Recruiting
Measuring Response of Adding Isosorbide Mononitrate to Misoprostol in Induction of Second Trimester Abortion[NCT03407521]	Phase 4	60 participants (Actual)	Interventional	2017-04-12	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Effect of Isosorbide Dinitrate on Central Venous Pressure

Determine effectiveness of study medication on hemodynamic profile by completing baseline and post-study medication maximal exercise tests to measure central venous pressure via IV catheter insertion (NCT04297241)
Timeframe: Baseline and 6 weeks

Intervention	mmHg (Median)
Isosorbide Dinitrate - Baseline	22.5
Isosorbide Dinitrate - Post-therapy	20.6

Effect of Isosorbide Dinitrate on Liver Stiffness Levels

Determine effectiveness of study medication on hemodynamic profile by completing baseline and post-study medication liver ultrasound measuring liver stiffness levels by sheer wave speed (m/s). (NCT04297241)
Timeframe: Baseline and 6 weeks

Intervention	m/s (Median)
Isosorbide Dinitrate - Baseline	2.3
Isosorbide Dinitrate - Post-therapy	2.1

Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Heart Rate Response

Obtain estimates of the effect the study medication has on maximal exercise test heart rate response in Fontan patients by study participants performing a maximal ramp exercise test on a stationary bike. (NCT04297241)
Timeframe: Baseline and 6 weeks

Intervention	bpm (Median)
Isosorbide Dinitrate - Baseline	156.6
Isosorbide Dinitrate - Post-therapy	164.7

Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Respiratory Rate Response

Obtain estimates of the effect the study medication has on maximal exercise test respiratory rate response in Fontan patients by study participants performing a maximal ramp exercise test on a stationary bike. (NCT04297241)
Timeframe: Baseline and 6 weeks

Intervention	Respiratory Exchange Ratio (Median)
Isosorbide Dinitrate - Baseline	1.17
Isosorbide Dinitrate - Post-therapy	1.19

Effect of Isosorbide Dinitrate on Maximal Exercise Capacity VO2 Max

Obtain estimates of the effect the study medication has on maximal exercise test VO2 max performance in Fontan patients by study participants performing a maximal ramp exercise test on a stationary bike. (NCT04297241)
Timeframe: Baseline and 6 weeks

Intervention	mL/min (Median)
Isosorbide Dinitrate - Baseline	1086.7
Isosorbide Dinitrate - Post-therapy	1151.3

Number of Participants Who Experience an Adverse Reaction to the Study Medication During the Study Enrollment Period.

Potential adverse side effects of study medication (isosorbide dinitrate) will be monitored throughout study period. Study medication will be titrated to a maximal dose of 30mg dependent on the patient tolerance. Patient tolerance is defined by frequency of known risk factors to the study medication (headaches, hypotension, and syncope). (NCT04297241)
Timeframe: Baseline and 6 weeks

Intervention	Participants (Count of Participants)
Isosorbide Dinitrate	16

Cesarean Delivery Rate

Rate of cesarean section for those enrolled in study (NCT03171480)
Timeframe: 7 days

Intervention	Participants (Count of Participants)
Monoket Pill	29
Placebo	22

Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid

placenta abruption at time of delivery, administration of IV antihypertensive medication for BP >160/110, maternal hypotensive defined as <90/50, Uterine hyperstimulation defined as >3 contractions in 10 minutes and meconium stained amniotic fluid anytime during labor induction/augmentation (NCT03171480)
Timeframe: during the induction of labor till delivery for all outcomes

Intervention	Participants (Count of Participants)
	Abruption	Anti-hypertensives	hypotension	uterine hyperstimulation	MSAF
Monoket Pill	0	29	9	3	0
Placebo Pill	0	32	8	1	0

Forearm Blood Flow (FBF)

Forearm blood flow was measured by strain gauge plethysmography (NCT00685945)
Timeframe: During and after each study drug administration

,,,

Intervention	ml/min/100ml (Mean)
	FBF (bradykinin 0 ng/min)	FBF (bradykinin 50ng/min)	FBF (bradykinin 100ng/min)	FBF (bradykinin 200 ng/min)
Control	4.03	7.02	13.17	17.74
Isosorbide + L-NMMA + Control	2.18	4.73	6.83	9.91
L-NMMA + Control	2.36	5.16	8.67	11.21
Sildenafil + L-NMMA + Control	2.80	5.87	9.13	12.92

Net Glucose Uptake

Individual net reuptake rates at each time point were calculated by the following formula: net uptake = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of glucose in the brachial vein and artery, respectively. (NCT00685945)
Timeframe: At baseline and after maximum dose of bradykinin

,,,

Intervention	microgram/min/100ml (Mean)
	Net glucose uptake (bradykinin 0 ng/min)	Net glucose uptake (bradykinin 200 ng/min)
Control	-79.95	-319.85
Isosorbide + L-NMMA + Control	-71.4	-163.233
L-NMMA + Control	-74.36	-142.86
Sildenafil + L-NMMA + Control	-67.3	-125.32

Net Tissue-type Plasminogen Activator (t-PA) Release

Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. (NCT00685945)
Timeframe: During and after each study drug administration

,,,

Intervention	ng/min/100ml (Mean)
	Net t-PA release (bradykinin 0ng/min)	Net t-PA release (bradykinin 50ng/min)	Net t-PA release (bradykinin 100ng/min)	Net t-PA release (bradykinin 200ng/min)
Control	0.24	1.02	11.81	30.03
Isosorbide + L-NMMA + Control	-0.38	3.14	15.90	45.32
L-NMMA + Control	0.59	3.65	22.10	39.90
Sildenafil + L-NMMA + Control	0.29	2.46	18.48	37.39

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT)

Steady state was defined as 90-120 minutes post-dose. NGT participants (FPG <100 mg/dL & 2 hour plasma glucose (PG) <140 mg/dL during a 75g oral glucose tolerance test (OGTT) at screening) were neither Impaired Glucose Tolerant (IGT) nor Impaired Fasting Glucose (IFG). IGT was defined as a 2 hour plasma glucose >= 140 and <= 199 mg/dL during a 75g oral glucose tolerance test at screening. IFG was defined as FPG between 100 and 125 mg/dL at screening. (NCT00871871)
Timeframe: 90 -120 minutes post-dose

Intervention	ng/minute (Least Squares Mean)
Hydrochlorothiazide (HCTZ)	5.54
Hydrochlorothiazide (HCTZ) Placebo	5.01

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG)

Steady state was defined as 90-120 minutes post-dose. IFG was defined as fasting plasma glucose (FPG) between 100 and 125 mg/dL at screening. (NCT00871871)
Timeframe: 90 -120 minutes post-dose

Intervention	ng/minute (Least Squares Mean)
Hydrochlorothiazide (HCTZ)	5.60
Hydrochlorothiazide (HCTZ) Placebo	4.50

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT)

Steady state was defined as 90-120 minutes post-dose. IGT was defined as a 2 hour plasma glucose >= 140 and <= 199 mg/dL during a 75g oral glucose tolerance test at screening. (NCT00871871)
Timeframe: 90 -120 minutes post-dose

Intervention	ng/minute (Least Squares Mean)
Hydrochlorothiazide (HCTZ)	3.44
Hydrochlorothiazide (HCTZ) Placebo	3.55

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG)

Steady state was defined as 90-120 minutes post-dose. The ratio was the quantity of glucose disposed by the body per kg body weight per minute at steady state divided by the approximate steady state plasma insulin concentration. The approximate steady state plasma insulin concentration was estimated by the time-weighted average of the insulin concentration measured at 10 minute intervals in which time = 90, 100, 110, and 120 minutes. IFG was defined as fasting plasma glucose (FPG) between 100 and 125 mg/dL at screening. (NCT00871871)
Timeframe: 90 -120 minutes post-dose

Intervention	(mg/kg/minute)/(µIU/mL) (Least Squares Mean)
Hydrochlorothiazide (HCTZ)	0.038
Hydrochlorothiazide (HCTZ) Placebo	0.037

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT)

Steady state was defined as 90-120 minutes post-dose. The ratio was the quantity of glucose disposed by the body per kg body weight per minute at steady state divided by the approximate steady state plasma insulin concentration. The approximate steady state plasma insulin concentration was estimated by the time-weighted average of the insulin concentration measured at 10 minute intervals in which time = 90, 100, 110, and 120 minutes. IGT was defined as a 2 hour plasma glucose >= 140 and <= 199 mg/dL during a 75g oral glucose tolerance test at screening. (NCT00871871)
Timeframe: 90 -120 minutes post-dose

Intervention	(mg/kg/minute)/(µIU/mL) (Least Squares Mean)
Hydrochlorothiazide (HCTZ)	0.061
Hydrochlorothiazide (HCTZ) Placebo	0.045

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT)

Steady state was defined as 90-120 minutes post-dose. The ratio was the measure of the quantity of glucose disposed per unit of plasma insulin concentration (PIC). Approximate PIC was estimated by the time-weighted average of the insulin concentration measured at 10 minute intervals, time = 90, 100, 110, and 120 minutes. NGT participants (FPG <100 mg/dL & 2 hour PG <140 mg/dL during a 75g OGTT at screening) were neither IGT nor IFG at screening. IGT - defined as a 2 hour PG >= 140 and <= 199 mg/dL during a 75g OGTT at screening. IFG - defined as FPG between 100 and 125 mg/dL at screening. (NCT00871871)
Timeframe: 90 -120 minutes post-dose

Intervention	(mg/kg/minute)/(µIU/mL) (Least Squares Mean)
Hydrochlorothiazide (HCTZ)	0.045
Hydrochlorothiazide (HCTZ) Placebo	0.042

Part II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state

Intervention	(mg/kg/minute)/(µIU/mL) (Least Squares Mean)
Isosorbide Mononitrate (ISMN)	0.040
Isosorbide Mononitrate (ISMN) Placebo	0.044

Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours

The number of patients requiring intubation was calculated based on the total number of mITT patients. (NCT00803634)
Timeframe: Initiation through termination of study drug (up to 96 hours)

Intervention	Patients (Number)
Clevidipine	0
Standard of Care	0

Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study

The percentage of patients in whom the SBP fell below the lower limit of the prespecified target range at any time during the entire study drug treatment period (up to 96 hours) was calculated within each treatment group using the number of mITT patients achieving the endpoint divided by the number of mITT patients and multiplied by 100. Two-tailed 95% CIs were computed for these percentages. (NCT00803634)
Timeframe: Initiation through termination of study drug (up to 96 hours)

Intervention	Percentage of patients (Number)
Clevidipine	68.2
Standard of Care	70.7

Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes

The percentage of patients in whom the SBP fell below the lower limit of the prespecified target range at any time during the first 30 minutes was calculated within each treatment group using the number of mITT patients achieving the endpoint divided by the number of mITT patients and multiplied by 100. Two-tailed 95% CIs were computed for these percentages. (NCT00803634)
Timeframe: Initiation of study drug through the initial 30-minutes

Intervention	Percentage of patients (Number)
Clevidipine	34.1
Standard of Care	2.4

Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment

The percentage of patients who received any alternative IV antihypertensive drug at any time during the study drug treatment period (up to 96 hours) was calculated using mITT patients within each treatment group. (NCT00803634)
Timeframe: Initiation through termination of study drug (up to 96 hours)

Intervention	Percentage of patients (Number)
Clevidipine	15.9
Standard of Care	51.2

Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours)

The percent of patients with at least one episode of SBP <90 mm Hg was calculated as the number of mITT patients who had at least one episode of SBP<90 mm Hg during study drug administration up to 96 hours divided by mITT patients, and multiplied by 100 for each treatment group. (NCT00803634)
Timeframe: Initiation through termination of study drug (up to 96 hours)

Intervention	Percentage of patients (Number)
Clevidipine	5.9
Standard of Care	1.9

Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes

The percentage of patients reaching this endpoint was calculated within each treatment group using the number of mITT patients reaching the endpoint divided by the number of mITT patients, and multiplied by 100. Two-tailed 95% CIs were computed for these percentages. (NCT00803634)
Timeframe: Initiation of study drug through the initial 30-minutes

Intervention	Percentage of patients (Number)
Clevidipine	45.5
SOC IV Therapy	51.2

Percentage to First Achieve Initial Prespecified SBP Target Range [≥20 mm Hg and ≤40 mm Hg Apart] and 15% Reduction From Baseline Within First 30 Minutes

Analysis of the percentage of patients achieving both components of this composite endpoint (attainment of the initial prespecified SBP target range and a 15% reduction in SBP from baseline) was calculated within each treatment group using the number of mITT patients achieving the SBP reduction goal divided by the number of mITT patients, and multiplied by 100. (NCT00803634)
Timeframe: Initiation of study drug through the initial 30-minutes

Intervention	Percentage of patients (Number)
Clevidipine	70.5
Standard of Care	36.6

SBP Area Under the Curve (AUC) Outside Prespecified Target Range

The magnitude and duration of SBP excursions was calculated as the area under the curve (AUC) for each patient, using the trapezoidal rule, related to time (in minutes) that each patient's SBP was outside the target range. AUC was determined based on data collected from the initiation of study medication through the end of monotherapy treatment up to 96 hours, normalized per hour, and expressed as mmHg × minute/hour. (NCT00803634)
Timeframe: Initiation of study drug through end of monotherapy (up to 96 hours)

Intervention	mm Hg x min/h (Mean)
Clevidipine	494.96
Standard of Care	966.15

Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes

Time to first achieve the initial pre-specified systolic blood pressure (SBP) target range and a 15% SBP reduction from baseline is the time in minutes between the initiation of study medication and the time the patient first achieved both components. Median time was estimated using Kaplan Meier method. 95% two-sided confidence interval of the median time is from 'Simon and Lee, 1982'. If patients did not reach both components within 30 minutes from the initial treatment with study medication, or another antihypertensive agent was administered, the patient was censored at 30 minutes or the time when another antihypertensive agent is given, whichever came first. (NCT00803634)
Timeframe: Initiation of study drug through the initial 30-minutes

Intervention	Minutes (Median)
Clevidipine	15.0
Standard of Care	NA

Time to Use Other IV Antihypertensives During the Study Drug Administration

The length of time to use other IV antihypertensive agents was defined as the duration in hours from the initiation of study drug through the time when any other concomitant IV antihypertensive agent was administered, thus, representing the time period without use of any other concomitant IV antihypertensive agent. Median time to use other IV antihypertensive agents was obtained using Kaplan-Meier method. If a patient did not receive any concomitant IV antihypertensive during the 96-hour treatment period, this patient was considered censored at 96 hours. If study drug was stopped less than 96 hours and the patient has no concomitant IV antihypertensive agent, the patient was considered censored when study drug was stopped. (NCT00803634)
Timeframe: Initiation of study drug through any other concomitant IV antihypertensive agent administered, up to 96 hours

Intervention	Hours (Median)
Clevidipine	NA
Standard of Care	5.7

Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point

A validated visual analog scale (VAS) with a horizontal ruler showing increments from 0 to 100 mm with 0 = Best and 100 = Worst was used. The test was asked from the patient's perspective and had to be administered with patient sitting. Relative change in VAS from baseline is the value at each time point minus the baseline value. Relative change from baseline was summarized descriptively (with associated two-tailed 95% CIs of the mean values) at 15, 30 and 45 minutes and at 1, 2, 3 hours and 12 hours, and 1 hour post termination of study drug treatment. (NCT00803634)
Timeframe: Baseline (immediately prior to study drug administration) through 1 hour after study drug termination

Intervention	millimeters (mm) (Mean)
	Baseline Through Initial 15 Min- CLV n=44;SOC n=38	Baseline Through Initial 30 Min- CLV n=43;SOC n=39	Baseline Through Initial 45 Min- CLV n=43;SOC n=39	Baseline Through Initial 1 H- CLV n=41;SOC n=38	Baseline Through Initial 2 H- CLV n=29;SOC n=29	Baseline Through Initial 3 H- CLV n=14;SOC n=22	Baseline Through Initial 12 H- CLV n=0;SOC n=7	Baseline Through 1 H Post Drug- CLV n=41;SOC n=33
Clevidipine	-18.6	-28.8	-37.1	-43.6	-45.2	-47.9	NA	-50.1
Standard of Care	-16.1	-22.8	-27.9	-34.6	-35.3	-40.5	-57.9	-50.1

Early Diastolic Mitral Annular Velocity

Diastolic mitral annular velocity measured at the basal septal mitral annulus (NCT01516346)
Timeframe: 24 weeks

Intervention	cm/s (Mean)
Isosorbide Dinitrate	6.8
Isosorbide Dinitrate + Hydralazine	7.3
Placebo	6.5

LV Mass

LV mass measured by MRI, in grams normalized to height in meters raised to the 1.7 power (m^1.7) (NCT01516346)
Timeframe: 24 weeks

Intervention	grams / meters ^1.7 (Mean)
Isosorbide Dinitrate	68.2
Isosorbide Dinitrate + Hydralazine	66.2
Placebo	67.2

Myocardial Extracellular Volume Fraction

Myocardial extracellular volume, expressed as percent of total tissue volume, measured by MRI (T1 mapping pre and post-gadolinium administration) (NCT01516346)
Timeframe: 24 weeks

Intervention	Percentage (Mean)
Isosorbide Dinitrate	29.0
Isosorbide Dinitrate + Hydralazine	31.3
Placebo	29.5

Quality of Life (Kansas City Cardiomyopathy Questionnaire Score)

Quality of life, assessed with the Kansas City cardiomyopathy questionnaire (overall summary score, which ranges from 0 to 100). Higher values imply better quality of life. (NCT01516346)
Timeframe: 24 weeks

Intervention	Points on a scale (Mean)
Isosorbide Dinitrate	62.1
Isosorbide Dinitrate + Hydralazine	44.9
Placebo	62.1

Wave Reflection Magnitude

The dimensionless ratio of backward (reflected) to forward wave amplitude. Higher values imply more wave reflection. (NCT01516346)
Timeframe: 24 weeks

Intervention	dimensionless ratio (Mean)
Isosorbide Dinitrate	0.38
Isosorbide Dinitrate + Hydralazine	0.44
Placebo	0.37

Cardiovascular Hospitalization

Number of Participants with acute coronary syndrome (ACS) or unstable angina (UA) (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	Participants (Count of Participants)
	Baseline	1 year
Pioglitazone + Standard Care	0	0
Standard Care	0	0

Carotic Atherosclerotic Lesions

Number of Participants with presence of atherosclerotic plaque of the intima media of common carotid artery greater than 1.4 mm (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	Participants (Count of Participants)
	Baseline	1 year
Pioglitazone + Standard Care	0	0
Standard Care	0	0

Coronary Artery Bypass [Coronary Revascularization]

Number of Participants with revascularization coronary procedures (coronary artery bypass grafting) (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	Participants (Count of Participants)
	Baseline	1 year
Pioglitazone + Standard Care	0	0
Standard Care	0	0

Diameter of Stenosis [Carotic Atherosclerotic Lesions]

Mean diameters of the stenosis of the right and left common carotid arteries (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	mm (Mean)
	Mean diameter of the stenosis of the right common carotid artery baseline	Mean diameter of the stenosis of the right common carotid artery in 1 year	Mean diameter of the stenosis of the left common carotid artery baseline	Mean diameter of the stenosis of the left common carotid artery in 1 year
Pioglitazone + Standard Care	9.8	5.0	11.6	4.1
Standard Care	8.7	4.8	10.1	5.6

Level of Insulin Resistance 1

Oral glucose tolerance test: number of Participants with impaired glucose tolerance (NCT03011775)
Timeframe: 6 months

Intervention	Participants (Count of Participants)
	Number of Participants with glucose level in the range of 7.8 to 11 mmol/L baseline	Number of Participants with glucose level in the range of 7.8 to 11 mmol/L in 6 month	Number of Participants with glucose level above 11 mmol/L baseline	Number of Participants with glucose level above 11 mmol/L in 6 month
Pioglitazone + Standard Care	7	13	10	5
Standard Care	14	16	4	3

Level of Insulin Resistance 2

Mean levels of blood glucose (NCT03011775)
Timeframe: Baseline and 6 months

Intervention	mmol/L (Mean)
	Baseline	In 6 month
Pioglitazone + Standard Care	6.0	5.97
Standard Care	5.9	5.60

Lipid Metabolism 1

Mean levels of total serum cholesterol (NCT03011775)
Timeframe: Baseline, 6 month and 1 year

Intervention	mmol / l (Mean)
	Mean values of the total cholesterol level baseline	Mean values of the total cholesterol level in 6 month	Mean values of the total cholesterol level in 1 year
Pioglitazone + Standard Care	5.27	4.5	4.5
Standard Care	5.28	4.3	4.3

Lipid Metabolism 2

Mean values of the triglyceride levels (NCT03011775)
Timeframe: Baseline, 6 month and 1 year

Intervention	1 mmol/L (Mean)
	Mean values of triglyceride baseline	Mean values of triglyceride in 6 month	Mean values of triglyceride in 1 year
Pioglitazone + Standard Care	0.69	0.72	0.9
Standard Care	0.61	0.73	0.7

Lipid Metabolism 3

Lipoproteine fractions:mean values of high-density lipoproteins and low density lipoproteins (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	mmol/L (Mean)
	Mean values of high-density lipoproteins in men baseline	Mean values of high-density lipoproteins in men in 1 year	Mean values of high-density lipoproteins in women baseline	Mean values of high-density lipoproteins in women in 1 year	Mean values of low density lipoproteins in men baseline	Mean values of low density lipoproteins in men in 1 year	Mean values of low density lipoproteins in women baseline	Mean values of low density lipoproteins in women in 1 year
Pioglitazone + Standard Care	0.8	1.1	0.9	1.2	3.9	2.9	4.5	3.3
Standard Care	0.9	1.0	1.1	1.0	4.4	3.0	3.5	2.7

Percutaneous Coronary Intervention [Coronary Revascularization]

Number of Participants with incidence of percutaneous coronary intervention. (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	Participants (Count of Participants)
	Baseline	1 year
Pioglitazone + Standard Care	0	0
Standard Care	0	0

Safety and Tolerability 1

Liver injury: mean values of ALT (NCT03011775)
Timeframe: Baseline, 6 month and 1 year

Intervention	units per liter (U/L) (Mean)
	Baseline	Mean values of ALT in 6 months	Mean values of ALT in 1 year
Pioglitazone + Standard Care	23.4	27.4	19.9
Standard Care	26.9	26.1	23.9

Safety and Tolerability 2

Liver injury: mean levels of total bilirubin (NCT03011775)
Timeframe: Baseline, 6 month and 1 year

Intervention	μmol/l (Mean)
	Baseline	Mean values of total bilirubin in 6 month	Mean values of total bilirubin in 1 year
Pioglitazone + Standard Care	12.3	12.4	15.7
Standard Care	10.8	12.7	15.0

Safety and Tolerability 3

Kidney injury: mean values of the microalbuminuria (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	mg/mol (Mean)
	Baseline	1 year
Pioglitazone + Standard Care	31.44	31.10
Standard Care	41.1	37.70

Safety and Tolerability 4

Kidneys injury: mean values of creatinine (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	μmol/l (Mean)
	Mean values of creatinine in men baseline	Mean values of creatinine in men in 1 year	Mean values of creatinine in women baseline	Mean values of creatinine in women in 1 year
Pioglitazone + Standard Care	105.6	85.0	66.8	72.5
Standard Care	102.3	82.0	88.2	77.5

Systemic Inflammation Level

Number of Participants with C-reactive protein level above 3 mg/L (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	Participants (Count of Participants)
	Baseline	In 1 year
Pioglitazone + Standard Care	10	12
Standard Care	7	13

Thickness of the Intima-media Complex

Mean thickness of carotid intima-media complex (NCT03011775)
Timeframe: Baseline, 6 month and 1 year

Intervention	cm (Mean)
	Mean thickness of the right carotid intima-media baseline	Mean thickness of the right carotid intima-media in 6 month	Mean thickness of the right carotid intima-media in 1 year	Mean thickness of the left carotid intima-media baseline	Mean thickness of the left carotid intima-media in 6 month	Mean thickness of the left carotid intima-media in 1 year
Pioglitazone + Standard Care	1.08	1.05	1.01	1.1	1.06	1.02
Standard Care	0.98	0.97	1.01	1.0	1.00	0.97

Сardiovascular Death

Number of Participants with cardiovascular death (NCT03011775)
Timeframe: Baseline and 1 year

Intervention	Participants (Count of Participants)
	Baseline	1 year
Pioglitazone + Standard Care	0	0
Standard Care	0	0

Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg + ISMN 60 mg Versus Single Dose of Placebo

"The augmentation index (AIx) is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P =~pressure and PP = Pulse Pressure. A mathematical transfer function translated the peripheral wave form into a central waveform using an FDA approved process based on directly recorded arterial pressure values. The mean AIx for each subject was estimated as a time-weighted average over the 10-hour post dose observation period and expressed as a change from baseline." (NCT00943852)
Timeframe: Baseline and 10 hours postdose

Intervention	Percent Change (Least Squares Mean)
Losartan 100 mg + ISMN 60 mg	-24.9
Placebo	-1.3

Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg Plus ISMN 60 mg Versus Single Dose of Losartan 100 mg

The augmentation index (AIx) is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. A mathematical transfer function translated the peripheral wave form into a central waveform using an FDA approved process based on directly recorded arterial pressure values. The mean AIx for each subject was estimated as a time-weighted average over the 10-hour post dose observation period and expressed as a change from baseline. (NCT00943852)
Timeframe: Baseline and 10 hours postdose

Intervention	Percent Change (Least Squares Mean)
Losartan 100 mg + ISMN 60 mg	-24.9
Losartan 100 mg	-1.8

Arbitrary Accelerometry Units (AAU) (Phase I)

To evaluate whether isosorbide mononitrate increases daily activity as assessed by 14-day averaged arbitrary accelerometry units in comparison to placebo. An arbitrary accelerometer unit is calculated within the accelerometer device that is worn by the patient and represents level of activity based on patient movement. Higher values indicate more movement. 0 indicates no movement. (NCT02053493)
Timeframe: 5-6 weeks

Intervention	accelerometry units (Mean)
Isosorbide Mononitrate Crossover to Placebo	9370
Placebo Crossover to Isosorbide Mononitrate	9538

Arbitrary Accelerometry Units (AAU) (Phase II)

Intervention	accelerometry units (Mean)
Isosorbide Mononitrate Crossover to Placebo	8824
Placebo Crossover to Isosorbide Mononitrate	8900

Borg Score During 6 Minute Walk Test (Phase I)

To evaluate whether isosorbide mononitrate improves quality of life in comparison to placebo. The Borg Scale consists of scale range of 0 to 10 (where 0 indicates no breathlessness at all and 10 indicates maximum breathlessness). Lower values are considered to be better than higher values. (NCT02053493)
Timeframe: Week 7

Intervention	units on a scale (Mean)
Isosorbide Mononitrate Crossover to Placebo	4.1
Placebo Crossover to Isosorbide Mononitrate	4.0

Borg Score During 6 Minute Walk Test (Phase II)

Intervention	units on a scale (Mean)
Isosorbide Mononitrate Crossover to Placebo	3.8
Placebo Crossover to Isosorbide Mononitrate	3.8

Improvement in Daily Activity - Area Under the Curve (Phase I)

To evaluate whether isosorbide mononitrate in comparison to placebo improves daily activity as measured by Area under the curve (AUC) of arbitrary accelerometry units during study drug administration. An arbitrary accelerometer unit is calculated within the accelerometer device that is worn by the patient and represents level of activity based on patient movement. Higher values indicate more movement. 0 indicates no movement. Area under the curve is defined as ((7*average acceleromtery units/day during 30 mg) + (7*average acceleromtery units/day during 60 mg) + (14*average acceleromtery units/day during 120 mg))/28 (NCT02053493)
Timeframe: 3-6 weeks

Intervention	accelerometry units (Mean)
Isosorbide Mononitrate Crossover to Placebo	9621.4
Placebo Crossover to Isosorbide Mononitrate	9714.0

Improvement in Daily Activity - Area Under the Curve (Phase II)

Intervention	accelerometry units (Mean)
Isosorbide Mononitrate Crossover to Placebo	9146.5
Placebo Crossover to Isosorbide Mononitrate	9325.9

Improvement in Daily Activity - Hours Active Per Day (Phase I)

To evaluate whether isosorbide mononitrate in comparison to placebo improves daily activity as measured by Hours active per day during maximal dose of study drug (NCT02053493)
Timeframe: 5-6 weeks

Intervention	Hours/day (Mean)
Isosorbide Mononitrate Crossover to Placebo	9.4
Placebo Crossover to Isosorbide Mononitrate	9.1

Improvement in Daily Activity - Hours Active Per Day (Phase II)

To evaluate whether isosorbide mononitrate in comparison to placebo improves daily activity as measured by Hours active per day during maximal dose of study drug (NCT02053493)
Timeframe: 11-12 weeks

Intervention	Hours/day (Mean)
Isosorbide Mononitrate Crossover to Placebo	9.4
Placebo Crossover to Isosorbide Mononitrate	8.8

Improvement in Daily Activity - Slope of Daily Average (Phase I)

To evaluate whether isosorbide mononitrate in comparison to placebo improves daily activity as measured by Slope of daily averaged arbitrary accelerometry units during study drug administration. An arbitrary accelerometer unit is calculated within the accelerometer device that is worn by the patient and represents level of activity based on patient movement. Higher values indicate more movement. 0 indicates no movement. (NCT02053493)
Timeframe: 3-6 weeks

Intervention	accelerometry units/day (Mean)
Isosorbide Mononitrate Crossover to Placebo	-3.4
Placebo Crossover to Isosorbide Mononitrate	-1.3

Improvement in Daily Activity - Slope of Daily Average (Phase II)

Intervention	accelerometry units/day (Mean)
Isosorbide Mononitrate Crossover to Placebo	2.6
Placebo Crossover to Isosorbide Mononitrate	-3.9

Kansas City Cardiomyopathy Questionnaire Overall Summary Score (Phase I)

To evaluate whether isosorbide mononitrate improves quality of life in comparison to placebo. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcomes measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Symptom Burden, Symptom Stability, Physical Limitation, Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scale and summary scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, fewer symptoms, better quality of life). (NCT02053493)
Timeframe: Week 7

Intervention	units on a scale (Mean)
Isosorbide Mononitrate Crossover to Placebo	57.3
Placebo Crossover to Isosorbide Mononitrate	64.2

Kansas City Cardiomyopathy Questionnaire Overall Summary Score (Phase II)

To evaluate whether isosorbide mononitrate improves quality of life in comparison to placebo. • The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcomes measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Symptom Burden, Symptom Stability, Physical Limitation, Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scale and summary scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, fewer symptoms, better quality of life).Higher values of the overall KCCQ score are considered to be better than lower values. (NCT02053493)
Timeframe: Week 13

Intervention	units on a scale (Mean)
Isosorbide Mononitrate Crossover to Placebo	59.1
Placebo Crossover to Isosorbide Mononitrate	61.6

N-terminal Pro-B-type Natriuretic Peptide Level (Phase I)

To evaluate whether isosorbide mononitrate improves natriuretic peptide levels in comparison to placebo (NCT02053493)
Timeframe: Week 7

Intervention	pg/mL (Mean)
Isosorbide Mononitrate Crossover to Placebo	513.0
Placebo Crossover to Isosorbide Mononitrate	542.4

N-terminal Pro-B-type Natriuretic Peptide Level (Phase II)

To evaluate whether isosorbide mononitrate improves natriuretic peptide levels in comparison to placebo (NCT02053493)
Timeframe: Week 13

Intervention	pg/mL (Mean)
Isosorbide Mononitrate Crossover to Placebo	466.1
Placebo Crossover to Isosorbide Mononitrate	573.3

Six Minute Walk Distance (Phase I)

To evaluate whether isosorbide mononitrate (ISMN) improves functional capacity by 6 minute walk distance in comparison to placebo. (NCT02053493)
Timeframe: Week 7

Intervention	meters (Mean)
Isosorbide Mononitrate Crossover to Placebo	307.8
Placebo Crossover to Isosorbide Mononitrate	327.1

Six Minute Walk Distance (Phase II)

To evaluate whether isosorbide mononitrate (ISMN) improves functional capacity by 6 minute walk distance in comparison to placebo. (NCT02053493)
Timeframe: Week 13

Intervention	meters (Mean)
Isosorbide Mononitrate Crossover to Placebo	321.3
Placebo Crossover to Isosorbide Mononitrate	329.7

Patient Preference for Isosorbide Mononitrate Treatment at the End of Study.

Self reported participant preference for study period 1 vs. study period 2. (NCT02053493)
Timeframe: Week 13

Intervention	participants (Number)
	Phase1	Phase2	No Preference
Isosorbide Mononitrate Crossover to Placebo	14	18	16
Placebo Crossover to Isosorbide Mononitrate	14	24	19

Biopsies

Histological changes in ulcers (NCT02789033)
Timeframe: 75 days

,,,

Intervention	UI/dL (Mean)
	α-smooth muscle actin	Von Willebrand Factor	vascular endothelial growth factor-A	desmin
Active Comparator: Chitosan	2.46	2.38	2.23	2.3
Active Comparator: Isosorbide Dinitrate Spray	2.64	2.28	2.6	2.5
Combination: IDS and Chitosan	2.56	2.31	2.43	2.6
Placebo Comparator: Placebo	2.07	2.15	2.07	2.3

Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment

(NCT04051957)
Timeframe: Baseline, Month 2

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	1
Placebo	0

Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment

(NCT04051957)
Timeframe: Baseline, Month 3

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	3
Placebo	1

Number of Participants With a Reduction in Urine Protein Creatinine Ratio (UPC) of > 500 mg/Day From That Measured Before Enrollment

(NCT04051957)
Timeframe: Baseline, Month 1

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	1
Placebo	0

Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Month 1

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	0
Placebo	0

Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Month 2

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	0
Placebo	0

Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Month 3

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	1
Placebo	0

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 1

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	0
Placebo	1

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 10

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	2
Placebo	2

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 11

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	3
Placebo	2

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 12

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	3
Placebo	2

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 2

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	2
Placebo	1

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 3

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	3
Placebo	1

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 4

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	4
Placebo	2

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 5

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	2
Placebo	1

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 6

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	3
Placebo	2

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 7

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	3
Placebo	2

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 8

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	3
Placebo	2

Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment

(NCT04051957)
Timeframe: Baseline, Week 9

Intervention	Participants (Count of Participants)
Isosorbide Mononitrate	3
Placebo	2

Condition	Relationship Strength	Studies	Trials
A-V Dissociation	medium	1	1
Achalasia	low	2	0
Achalasia, Esophageal	low	2	0
Acoustic Trauma	low	1	0
Acrania	low	1	0
Acute Confusional Senile Dementia	low	1	0
Acute Disease	low	4	0
Acute Kidney Failure	medium	1	1
Acute Kidney Injury	medium	1	1
Acute Kidney Insufficiency	medium	1	1
Acute Liver Injury, Drug-Induced	low	1	0
Acute Post-operative Pain	low	1	0
Acute Postoperative Pain	low	1	0
Acute Renal Failure	medium	1	1
Acute Renal Injury	medium	1	1
Acute Renal Insufficiency	medium	1	1
Adjustment Disorder	low	1	0
Adjustment Disorders	low	1	0
Adverse Drug Event	low	2	0
Adverse Drug Reaction	low	2	0
Aging	medium	1	1
Agnogenic Myeloid Metaplasia	low	1	0
Allodynia	low	1	0
Allodynia, Mechanical	low	1	0
Allodynia, Tactile	low	1	0
Allodynia, Thermal	low	1	0
Alloxan Diabetes	low	1	0
Alveolar Bone Atrophy	low	1	0
Alveolar Bone Loss	low	1	0
Alveolar Process Atrophy	low	1	0
Alveolar Resorption	low	1	0
Alzheimer Dementia	low	1	0
Alzheimer Disease	low	1	0
Alzheimer Disease, Early Onset	low	1	0
Alzheimer Disease, Late Onset	low	1	0
Alzheimer Sclerosis	low	1	0
Alzheimer Syndrome	low	1	0
Alzheimer Type Senile Dementia	low	1	0
Alzheimer-Type Dementia (ATD)	low	1	0
Alzheimer's Disease	low	1	0
Alzheimer's Disease, Focal Onset	low	1	0
Alzheimer's Diseases	low	1	0
Amentia	low	1	0
American Trypanosomiasis	low	1	0
Anasarca	low	2	0
Angina at Rest	medium	2	1
Angina Pectoris	medium	20	5
Angina Pectoris, Unstable	medium	2	1
Angina Pectoris, Variant	low	3	0
Angina, Preinfarction	medium	2	1
Angina, Unstable	medium	2	1
Angiogenesis, Pathologic	low	1	0
Angiogenesis, Pathological	low	1	0
Angor Pectoris	medium	20	5
Anniversary Reaction	low	1	0
Anterior Choroidal Artery Infarction	low	1	0
Aphthae	medium	1	1
Apoplexy	low	1	0
Aqueductal Stenosis	medium	9	2
Arrhythmia	medium	1	1
Arrhythmias, Cardiac	medium	1	1
Arrythmia	medium	1	1
Arteriosclerosis, Coronary	low	1	0
Arthropathies	low	1	0
Asthma	low	1	0
Asthma, Bronchial	low	1	0
Atherosclerosis, Coronary	low	1	0
Atrial Fibrillation	medium	2	1
Atrial Flutter	low	1	0
Atrioventricular Dissociation	medium	1	1
Atrioventricular Nodal Re-Entrant Tachycardia	low	1	0
Atrioventricular Reentrant Tachycardia	low	1	0
Auditory Vertigo	medium	16	1
Aural Vertigo	medium	16	1
Auricular Fibrillation	medium	2	1
Auricular Flutter	low	1	0
Auriculo-Ventricular Dissociation	medium	1	1
Autoimmune Disease	low	1	0
Autoimmune Diseases	low	1	0
Blood Clot	low	1	0
Blood Pressure, High	medium	2	1
Blood Pressure, Low	low	2	0
Body Weight	medium	1	1
Bone Loss, Alveolar	low	1	0
Bone Loss, Periodontal	low	1	0
Bone Marrow Fibrosis	low	1	0
Brain Diseases	low	1	0
Brain Disorders	low	1	0
Brain Hemorrhage, Cerebral	low	1	0
Brain Vascular Disorders	low	1	0
Bronchial Asthma	low	1	0
Burns	low	1	0
Canine Diseases	low	2	0
Canker Sore	medium	1	1
Carcinogenesis	low	1	0
Carcinoma, Basal Cell	low	1	0
Carcinoma, Basal Cell, Pigmented	low	1	0
Cardiac Arrhythmia	medium	1	1
Cardiac Arrhythmias	medium	1	1
Cardiac Diseases	medium	1	1
Cardiac Disorders	medium	1	1
Cardiac Dysrhythmia	medium	1	1
Cardiac Failure	medium	12	3
Cardiac Output, Low	low	1	0
Cardiomyopathy, Congestive	low	1	0
Cardiomyopathy, Dilated	low	1	0
Cardiomyopathy, Dilated, 1a	low	1	0
Cardiomyopathy, Dilated, Autosomal Recessive	low	1	0
Cardiomyopathy, Dilated, CMD1A	low	1	0
Cardiomyopathy, Dilated, LMNA	low	1	0
Cardiomyopathy, Dilated, With Conduction Defect 1	low	1	0
Cardiomyopathy, Dilated, with Conduction Deffect1	low	1	0
Cardiomyopathy, Familial Idiopathic	low	1	0
Cardiomyopathy, Idiopathic Dilated	low	1	0
Cardiospasm	low	2	0
Cardiovascular Diseases	medium	2	1
Cardiovascular Stroke	medium	4	2
Cat Diseases	low	1	0
Cell Transformation, Neoplastic	low	1	0
Central Hypothyroidism	low	1	0
Central Nervous System Disorders, Intracranial	low	1	0
Central Nervous System Intracranial Disorders	low	1	0
Central Nervous System Origin Vertigo	low	5	0
Cerebral Hemorrhage	low	1	0
Cerebral Infarct	low	1	0
Cerebral Infarction	low	1	0
Cerebral Infarction, Left Hemisphere	low	1	0
Cerebral Infarction, Right Hemisphere	low	1	0
Cerebral Parenchymal Hemorrhage	low	1	0
Cerebral Stroke	low	1	0
Cerebral Ventriculomegaly	medium	9	2
Cerebral, Left Hemisphere, Infarction	low	1	0
Cerebral, Right Hemisphere, Infarction	low	1	0
Cerebrovascular Accident	low	1	0
Cerebrovascular Accident, Acute	low	1	0
Cerebrovascular Apoplexy	low	1	0
Cerebrovascular Diseases	low	1	0
Cerebrovascular Disorders	low	1	0
Cerebrovascular Insufficiency	low	1	0
Cerebrovascular Occlusion	low	1	0
Cerebrovascular Stroke	low	1	0
Chagas Disease	low	1	0
Chagas' Disease	low	1	0
Chemical and Drug Induced Liver Injury	low	1	0
Chemically-Induced Liver Toxicity	low	1	0
Chronic Disease	low	2	0
Chronic Idiopathic Myelofibrosis	low	1	0
Chronic Illness	low	2	0
Chronic Kidney Diseases	medium	1	1
Chronic Kidney Insufficiency	medium	1	1
Chronic Post-operative Pain	low	1	0
Chronic Post-surgical Pain	low	1	0
Chronic Postoperative Pain	low	1	0
Chronic Postsurgical Pain	low	1	0
Chronic Renal Diseases	medium	1	1
Chronic Renal Insufficiency	medium	1	1
Chronically Ill	low	2	0
Cirrhosis, Liver	low	1	0
Cleft Spine	medium	2	1
CNS Disorders, Intracranial	low	1	0
CNS Origin Vertigo	low	5	0
Cochlear Hearing Loss	low	6	0
Communicating Hydrocephalus	medium	9	2
Complication, Postoperative	medium	2	1
Complications of Diabetes Mellitus	low	1	0
Congenital Hydrocephalus	medium	9	2
Congenital Zika Syndrome	low	1	0
Congenital Zika Virus Infection	low	1	0
Congestive Cardiomyopathy	low	1	0
Congestive Heart Failure	medium	12	3
Constriction, Pathologic	low	1	0
Constriction, Pathological	low	1	0
Contact Dermatitis	low	1	0
Coronary Arteriosclerosis	low	1	0
Coronary Artery Disease	low	1	0
Coronary Artery Stenosis	low	1	0
Coronary Artery Vasospasm	low	6	0
Coronary Atherosclerosis	low	1	0
Coronary Disease	medium	10	6
Coronary Heart Disease	medium	10	6
Coronary Stenoses	low	1	0
Coronary Stenosis	low	1	0
Coronary Vasospasm	low	6	0
Craniofacial Pain	medium	1	1
Craniorachischisis	low	1	0
CVA (Cerebrovascular Accident)	low	1	0
Deafness Neurosensory	low	6	0
Deglutition Disorders	low	1	0
Dehydration	low	2	0
Dementia	low	1	0
Dementia, Alzheimer Type	low	1	0
Dementia, Presenile	low	1	0
Dementia, Primary Senile Degenerative	low	1	0
Dementia, Senile	low	1	0
Dentin Hypersensitivity	medium	1	1
Dentin Sensitivity	medium	1	1
Dentine Hypersensitivity	medium	1	1
Dentine Sensitivity	medium	1	1
Depression, Reactive	low	1	0
Dermatitis Venenata	low	1	0
Dermatitis, Atopic	medium	4	1
Dermatitis, Contact	low	1	0
Developmental Defects, Neural Tube	low	1	0
Developmental Neural Tube Defects	low	1	0
Diabetes Complications	low	1	0
Diabetes Mellitus	low	1	0
Diabetes Mellitus, Experimental	low	1	0
Diabetes-Related Complications	low	1	0
Diabetic Complications	low	1	0
Diarrhea	medium	1	1
Diastematomyelia	low	1	0
Dihydropyrimidine Dehydrogenase Deficiency	low	1	0
Dihydropyrimidinuria	low	1	0
Dilated Cardiomyopathy	low	1	0
Disease Models, Animal	low	5	0
Distorted Hearing	medium	1	1
Dizziness	low	1	0
Dizzyness	low	1	0
Dog Diseases	low	2	0
DPD Deficiency	low	1	0
Drop Attack	low	1	0
Dropsy	low	2	0
Drug Side Effects	low	2	0
Drug Toxicity	low	2	0
Drug-Induced Acute Liver Injury	low	1	0
Drug-Induced Liver Disease	low	1	0
Drug-Induced Liver Injury	low	1	0
Drug-Related Side Effects and Adverse Reactions	low	2	0
Dysacusis	medium	1	1
Dysphagia	low	1	0
Ear Diseases	low	1	0
Early Onset Alzheimer Disease	low	1	0
Eczema, Atopic	medium	4	1
Eczema, Contact	low	1	0
Eczema, Infantile	medium	4	1
Edema	low	2	0
Edema-Proteinuria-Hypertension Gestosis	medium	1	1
Emergencies	low	1	0
Emesis	medium	2	1
Encephalon Diseases	low	1	0
Encephalopathy	low	1	0
Endolymphatic Hydrops	medium	8	1
EPH Complex	medium	1	1
EPH Gestosis	medium	1	1
EPH Toxemias	medium	1	1
Epithelioma, Basal Cell	low	1	0
Esophageal Achalasia	low	2	0
Esophageal and Gastric Varices	low	4	0
Esophageal Diseases	low	1	0
Esophageal Dysphagia	low	1	0
Esophageal Varices	low	4	0
Esophageal Varix	low	4	0
Exencephaly	low	1	0
Experimental Diabetes Mellitus	low	1	0
Experimental Neoplasms	low	1	0
Extravascular Hemolysis	low	1	0
Eye Diseases	low	1	0
Eye Disorders	low	1	0
Face Pain	medium	1	1
Facial Neoplasms	low	1	0
Facial Pain	medium	1	1
Fainting	low	1	0
Familial Alzheimer Disease (FAD)	low	1	0
Familial Atrial Fibrillation	medium	2	1
Familial Dementia	low	1	0
Familial Pyrimidemia	low	1	0
Familial Pyrimidinemia	low	1	0
Feline Diseases	low	1	0
Fetal Cerebral Ventriculomegaly	medium	9	2
Fever, Zika	low	1	0
Fibrosis, Bone Marrow	low	1	0
Fibrosis, Liver	low	1	0
Focal Onset Alzheimer's Disease	low	1	0
Gasser Syndrome	low	1	0
Gasser's Syndrome	low	1	0
Gastric Varices	low	4	0
Gastric Varix	low	4	0
Gastrointestinal Hemorrhage	low	3	0
Gestosis, EPH	medium	1	1
Glaucoma	medium	5	1
Graft vs Host Disease	low	1	0
Graft-Versus-Host Disease	low	1	0
Graft-vs-Host Disease	low	1	0
Haemolysis	low	1	0
Hearing Disorders	medium	1	1
Hearing Loss, Cochlear	low	6	0
Hearing Loss, Noise-Induced	low	1	0
Hearing Loss, Sensorineural	low	6	0
Heart Attack	medium	4	2
Heart Block	medium	1	1
Heart Decompensation	medium	12	3
Heart Disease, Ischemic	medium	4	1
Heart Diseases	medium	1	1
Heart Disorders	medium	1	1
Heart Failure	medium	12	3
Heart Failure, Congestive	medium	12	3
Heart Failure, Left-Sided	medium	12	3
Heart Failure, Right-Sided	medium	12	3
Heart Valve Diseases	medium	1	1
Heart Valvular Disease	medium	1	1
Hematochezia	low	3	0
Hemolysis	low	1	0
Hemolytic-Uremic Syndrome	low	1	0
Hemorrhage, Cerebral	low	1	0
Hemorrhage, Cerebrum	low	1	0
Hemorrhage, Gastrointestinal	low	3	0
Hepatic Cirrhosis	low	1	0
Hepatitis, Drug-Induced	low	1	0
Hepatitis, Toxic	low	1	0
Hereditary Thymine-Uraciluria	low	1	0
Homologous Wasting Disease	low	1	0
Hydrocephalus	medium	9	2
Hydrocephalus Ex-Vacuo	medium	9	2
Hydrocephaly	medium	9	2
Hydrops	low	2	0
Hyperalgesia	low	1	0
Hyperalgesia, Mechanical	low	1	0
Hyperalgesia, Primary	low	1	0
Hyperalgesia, Secondary	low	1	0
Hyperalgesia, Tactile	low	1	0
Hyperalgesia, Thermal	low	1	0
Hyperalgesic Sensations	low	1	0
Hyperalgia	low	1	0
Hyperalgia, Mechanical	low	1	0
Hyperalgia, Primary	low	1	0
Hyperalgia, Secondary	low	1	0
Hyperglycemia	low	1	0
Hyperglycemia, Postprandial	low	1	0
Hypermelanosis	low	1	0
Hypernatremia	medium	1	1
Hyperpigmentation	low	1	0
Hypersensitivity, Contact	low	1	0
Hypertension-Edema-Proteinuria Gestosis	medium	1	1
Hypertension, Pulmonary	low	1	0
Hypotension	low	2	0
Hypotension, Vascular	low	2	0
Hypothyroidism	low	1	0
Icterus	low	1	0
Idiopathic Myelofibrosis	low	1	0
Idiopathic Ventricular Tachycardia	low	1	0
Impotence, Arteriogenic	medium	1	1
Impotence, Vasculogenic	medium	1	1
Impotence, Venogenic	medium	1	1
Infant, Premature, Diseases	low	1	0
Infarction, Cerebral	low	1	0
Infarction, Cerebral, Left Hemisphere	low	1	0
Infarction, Cerebral, Right Hemisphere	low	1	0
Infarction, Left Hemisphere, Cerebral	low	1	0
Infarction, Right Hemisphere, Cerebral	low	1	0
Inflammation, Endodontic	medium	1	1
Iniencephaly	low	1	0
Intracerebral Hemorrhage	low	1	0
Intracranial Central Nervous System Disorders	low	1	0
Intracranial CNS Disorders	low	1	0
Intracranial Vascular Disorders	low	1	0
Intraocular Pressure	medium	3	1
Intravascular Hemolysis	low	1	0
Ischemia, Myocardial	medium	4	1
Ischemic Heart Disease	medium	4	1
Jaundice	low	1	0
Jaundice, Hemolytic	low	1	0
Joint Diseases	low	1	0
Kidney Diseases	low	2	0
Kidney Failure, Acute	medium	1	1
Kidney Insufficiency, Acute	medium	1	1
Kidney Insufficiency, Chronic	medium	1	1
Late Onset Alzheimer Disease	low	1	0
Left Hemisphere, Cerebral Infarction	low	1	0
Left Hemisphere, Infarction, Cerebral	low	1	0
Left Main Coronary Artery Disease	low	1	0
Left Main Coronary Disease	low	1	0
Left Main Disease	low	1	0
Left Ventricular Dysfunction	low	1	0
Left-Sided Heart Failure	medium	12	3
Light-Headedness	low	1	0
Lightheadedness	low	1	0
Liver Cirrhosis	low	1	0
Liver Fibrosis	low	1	0
Liver Injury, Drug-Induced	low	1	0
Liver Injury, Drug-Induced, Acute	low	1	0
Low Blood Pressure	low	2	0
Low Cardiac Output	low	1	0
Low Cardiac Output Syndrome	low	1	0
Mechanical Allodynia	low	1	0
Mechanical Hyperalgesia	low	1	0
Megaesophagus	low	2	0
Meniere Disease	medium	16	1
Meniere's Disease	medium	16	1
Meniere's Syndrome	medium	16	1
Mitral Incompetence	low	1	0
Mitral Insufficiency	low	1	0
Mitral Regurgitation	low	1	0
Mitral Valve Incompetence	low	1	0
Mitral Valve Insufficiency	low	1	0
Mitral Valve Regurgitation	low	1	0
Mu00E9niu00E8re Disease	medium	16	1
Mu00E9niu00E8re's Disease	medium	16	1
Mu00E9niu00E8re's Vertigo	medium	16	1
Muscle Contraction	low	1	0
Myelofibrosis	low	1	0
Myelofibrosis With Myeloid Metaplasia	low	1	0
Myeloid Metaplasia	low	1	0
Myelosclerosis	low	1	0
Myelosis, Nonleukemic	low	1	0
Myocardial Failure	medium	12	3
Myocardial Infarct	medium	4	2
Myocardial Infarction	medium	4	2
Myocardial Ischemia	medium	4	1
Myocardial Preinfarction Syndrome	medium	2	1
Myofacial Pain	medium	1	1
Myxedema	low	1	0
Neoplasms, Experimental	low	1	0
Neoplastic Cell Transformation	low	1	0
Neoplastic Transformation, Cell	low	1	0
Neovascularization, Pathologic	low	1	0
Neovascularization, Pathological	low	1	0
Neural Tube Defects	low	1	0
Neural Tube Developmental Defects	low	1	0
Neuralgic Facial Pain	medium	1	1
Neurally Mediated Faint	low	1	0
Neurenteric Cyst	low	1	0
Neurodermatitis, Atopic	medium	4	1
Neurodermatitis, Disseminated	medium	4	1
Neuroenteric Cyst	low	1	0
Nonsustained Ventricular Tachycardia	low	1	0
Obstructive Hydrocephalus	medium	9	2
Occult Spinal Dysraphism	low	1	0
Occult Spinal Dysraphism Sequence	low	1	0
Oncogenesis	low	1	0
Open Spine	medium	2	1
Orofacial Pain	medium	1	1
Oropharyngeal Dysphagia	low	1	0
Orthostasis	low	1	0
Otogenic Vertigo	medium	16	1
Otologic Diseases	low	1	0
Otological Diseases	low	1	0
Pain, Facial	medium	1	1
Pain, Post-operative	low	1	0
Pain, Postoperative	low	1	0
Paracousis	medium	1	1
Paracusis	medium	1	1
Paroxysmal Atrial Fibrillation	medium	2	1
Paroxysmal Supraventricular Tachycardia	low	1	0
Pathologic Angiogenesis	low	1	0
Pathologic Constriction	low	1	0
Pathologic Neovascularization	low	1	0
Periadenitis Mucosa Necrotica Recurrens	medium	1	1
Pericementitis	low	1	0
Periodontal Bone Loss	low	1	0
Periodontal Resorption	low	1	0
Periodontitis	low	1	0
Peritonitis	low	1	0
Persistent Atrial Fibrillation	medium	2	1
Persistent Postsurgical Pain	low	1	0
Polychondritis, Chronic Atrophic	low	1	0
Polychondritis, Relapsing	low	1	0
Positional Vertigo	low	5	0
Post-operative Pain	low	1	0
Post-operative Pain, Acute	low	1	0
Post-operative Pain, Chronic	low	1	0
Post-surgical Pain	low	1	0
Post-Traumatic Hydrocephalus	medium	9	2
Posterior Choroidal Artery Infarction	low	1	0
Postoperative Complications	medium	2	1
Postoperative Pain	low	1	0
Postoperative Pain, Acute	low	1	0
Postoperative Pain, Chronic	low	1	0
Postprandial Hyperglycemia	low	1	0
Postsurgical Pain	low	1	0
Pre-Eclampsia	medium	1	1
Preeclampsia	medium	1	1
Preeclampsia Eclampsia 1	medium	1	1
Pregnancy	medium	2	1
Pregnancy Toxemias	medium	1	1
Presenile Alzheimer Dementia	low	1	0
Presyncope	low	1	0
Primary Hypothyroidism	low	1	0
Primary Myelofibrosis	low	1	0
Primary Peritonitis	low	1	0
Primary Senile Degenerative Dementia	low	1	0
Prinzmetal Angina	low	3	0
Prinzmetal's Angina	low	3	0
Proteinuria	medium	1	1
Proteinuria-Edema-Hypertension Gestosis	medium	1	1
Psychoses, Drug	low	1	0
Psychoses, Substance-Induced	low	1	0
Psychoses, Toxic	low	1	0
Pulmonary Hypertension	low	1	0
Pulpitis	medium	1	1
Pulsatile Tinnitus	low	2	0
Pyrimidinemia, Familial	low	1	0
Rachischisis	medium	2	1
Reactive Disorders	low	1	0
Recrudescence	low	4	0
Recurrence	low	4	0
Relapse	low	4	0
Renal Failure, Acute	medium	1	1
Renal Insufficiency, Acute	medium	1	1
Renal Insufficiency, Chronic	medium	1	1
Right Hemisphere, Cerebral Infarction	low	1	0
Right Hemisphere, Infarction, Cerebral	low	1	0
Right-Sided Heart Failure	medium	12	3
Ringing-Buzzing-Tinnitus	low	2	0
Rodent Ulcer	low	1	0
Runt Disease	low	1	0
Rupture	low	1	0
Schistorrhachis	medium	2	1
Secondary Hypothyroidism	low	1	0
Secondary Peritonitis	low	1	0
Senile Dementia, Acute Confusional	low	1	0
Senile Dementia, Alzheimer Type	low	1	0
Senile Paranoid Dementia	low	1	0
Sensitivity and Specificity	low	3	0
Sensitivity, Contact	low	1	0
Sensorineural Hearing Loss	low	6	0
Side Effects of Drugs	low	2	0
Spina Bifida	medium	2	1
Spinal Cord Myelodysplasia	low	1	0
Spinal Dysraphia	medium	2	1
Spinal Dysraphism	medium	2	1
Spinning Sensation	low	5	0
Spontaneous Oto-Acoustic Emission Tinnitus	low	2	0
Status Dysraphicus	medium	2	1
Stenocardia	medium	20	5
Stenosis	low	1	0
Stomatitis, Aphthous	medium	1	1
Streptozocin Diabetes	low	1	0
Streptozotocin Diabetes	low	1	0
Stricture	low	1	0
Stroke	low	1	0
Stroke, Acute	low	1	0
Subcortical Infarction	low	1	0
Substance-Induced Psychoses	low	1	0
Swallowing Disorders	low	1	0
Symptom Cluster	low	1	0
Syncopal Episode	low	1	0
Syncopal Vertigo	low	1	0
Syncope	low	1	0
Syncope, Cardiogenic	low	1	0
Syncope, Carotid Sinus	low	1	0
Syncope, Cerebral	low	1	0
Syncope, Convulsive	low	1	0
Syncope, Deglutitional	low	1	0
Syncope, Effort	low	1	0
Syncope, Hyperventilation	low	1	0
Syncope, Malignant Neurocardiogenic	low	1	0
Syncope, Micturition	low	1	0
Syncope, Neurocardiogenic	low	1	0
Syncope, Neurogenic	low	1	0
Syncope, Postural	low	1	0
Syncope, Situational	low	1	0
Syncope, Stokes-Adams	low	1	0
Syncope, Supine	low	1	0
Syncope, Tussive	low	1	0
Syncope, Vasodepressor	low	1	0
Syncope, Vasovagal	low	1	0
Syncope, Vasovagal, Neurally-Mediated	low	1	0
Syndrome	low	1	0
Tachyarrhythmia	medium	3	2
Tachycardia	medium	3	2
Tachycardia, Ventricular	low	1	0
Tactile Allodynia	low	1	0
Tensor Palatini Induced Tinnitus	low	2	0
Tensor Tympani Induced Tinnitus	low	2	0
Tethered Cord Syndrome	low	1	0
Tethered Spinal Cord Syndrome	low	1	0
Thermal Allodynia	low	1	0
Thrombosis	low	1	0
Thrombus	low	1	0
Thymine-Uraciluria, Hereditary	low	1	0
Thyroid-Stimulating Hormone Deficiency	low	1	0
Tinnitus	low	2	0
Tinnitus of Vascular Origin	low	2	0
Tinnitus, Clicking	low	2	0
Tinnitus, Leudet	low	2	0
Tinnitus, Leudet's	low	2	0
Tinnitus, Noise Induced	low	2	0
Tinnitus, Objective	low	2	0
Tinnitus, Spontaneous Oto-Acoustic Emission	low	2	0
Tinnitus, Subjective	low	2	0
Tinnitus, Tensor Palatini Induced	low	2	0
Tinnitus, Tensor Tympani Induced	low	2	0
Tooth Sensitivity	medium	1	1
Toxemia Of Pregnancy	medium	1	1
Toxemias, Pregnancy	medium	1	1
Toxic Hepatitis	low	1	0
Toxic Psychoses	low	1	0
Toxicity, Drug	low	2	0
Transformation, Neoplastic Cell	low	1	0
Transient Situational Disturbance	low	1	0
Trypanosoma cruzi Infection	low	1	0
Trypanosomiasis, South American	low	1	0
TSH Deficiency	low	1	0
Tumorigenesis	low	1	0
Tumorigenic Transformation	low	1	0
Ulcer, Aphthous	medium	1	1
Ulcer, Rodent	low	1	0
Unstable Angina	medium	2	1
Ureteral Calculi	medium	1	1
Ureteral Calculus	medium	1	1
Valvular Heart Diseases	medium	1	1
Vascular Accident, Brain	low	1	0
Vascular Diseases	low	1	0
Vascular Diseases, Intracranial	low	1	0
Vascular Hypotension	low	2	0
Vascular Origin Tinnitus	low	2	0
Venous Leakage, Penile	medium	1	1
Ventricular Dysfunction, Left	low	1	0
Ventricular Tachyarrhythmias	low	1	0
Ventricular Tachycardia	low	1	0
Vertigo	low	5	0
Vertigo, Aural	medium	16	1
Vertigo, Brain Stem	low	5	0
Vertigo, Brainstem	low	5	0
Vertigo, Central Nervous System Origin	low	5	0
Vertigo, Central Origin	low	5	0
Vertigo, Constant	low	5	0
Vertigo, Essential	low	5	0
Vertigo, Intermittant	low	5	0
Vertigo, Paroxysmal	low	5	0
Vertigo, Peripheral	low	5	0
Vertigo, Subjective	low	5	0
Vomiting	medium	2	1
Water Stress	low	2	0
Zika Fever	low	1	0
Zika Virus Disease	low	1	0
Zika Virus Infection	low	1	0
ZikV Infection	low	1	0

Article	Year
An outbreak of pyrimethamine toxicity in patients with ischaemic heart disease in Pakistan. Basic & clinical pharmacology & toxicology, Volume: 115, Issue: 3	2014
Organic solvents as vehicles for precipitating liquid embolics: a comparative angiotoxicity study with superselective injections of swine rete mirabile. AJNR. American journal of neuroradiology, Volume: 27, Issue: 9	2006
Effect of osmotic diuresis on gentamicin-induced nephrotoxicity in rats. Archives of toxicology, Volume: 45, Issue: 3	1980
Experimental gentamicin nephrotoxicity: effect of streptozotocin-induced diabetes. The Journal of pharmacology and experimental therapeutics, Volume: 233, Issue: 1	1985
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
[The acute and chronic effects of 50 mg of isosorbide 5-mononitrate with delayed action in patients with stable angina of effort]. Revista espanola de cardiologia, Volume: 45, Issue: 2	1992
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Quantification of myo-inositol, 1,5-anhydro- D-sorbitol, and D-chiro-inositol using high-performance liquid chromatography with electrochemical detection in very small volume clinical samples. Biomedical chromatography : BMC, Volume: 29, Issue: 11	2015
Acute effect of ibopamine and isosorbide mononitrate on blood volume distribution in congestive heart failure. European journal of clinical pharmacology, Volume: 47, Issue: 4	1994
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Retarder action of isosorbide in a microemulsion for a targeted delivery of ceramide NP into the Die Pharmazie, Aug-01, Volume: 72, Issue: 8	2017
Isosorbide-Induced Decompression Effect on the Scala Media: Participation of Plasma Osmolality and Plasma Arginine Vasopressin. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, Volume: 38, Issue: 4	2017
Effects of oral isosorbide and glycerol on intraocular pressure, serum osmolality, and blood glucose in normal dogs. Veterinary ophthalmology, Volume: 16, Issue: 1	2013
FDA-approved drug labeling for the study of drug-induced liver injury. Drug discovery today, Volume: 16, Issue: 15-16	2011
Single oral dose study of two isosorbide-based aspirin prodrugs in the dog. The Journal of pharmacy and pharmacology, Volume: 55, Issue: 10	2003
Medical treatment of myocardial ischemia in coronary artery disease: effect of drug regime and irregular dosing in the CAPE II trial. Journal of the American College of Cardiology, Sep-04, Volume: 40, Issue: 5	2002
Isosorbide in the management of infantile hydrocephalus. Developmental medicine and child neurology, Volume: 25, Issue: 4	1983
Agreement and reproducibility of the estimates of cardiovascular function by impedance cardiography and M-mode echocardiography in healthy subjects. British journal of clinical pharmacology, Volume: 34, Issue: 1	1992
Isosorbide in treatment of infantile hydrocephalus. Archives of disease in childhood, Volume: 50, Issue: 6	1975
Propranolol in the treatment of angina: a review. Postgraduate medical journal, Volume: 52 Suppl 4	1976
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Prevention of contrast-induced nephropathy by adequate hydration combined with isosorbide dinitrate for patients with renal insufficiency and congestive heart failure. Clinical cardiology, Volume: 42, Issue: 1	2019
Comparative electrophysiological effects of captopril or hydralazine combined with nitrate in patients with left ventricular dysfunction and inducible ventricular tachycardia. British heart journal, Volume: 67, Issue: 5	1992
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

isosorbide

Description

Cross-References

Synonyms (105)

Research Excerpts

Overview

Drug Classes (1)

Protein Targets (3)

Potency Measurements

Bioassays (38)

Research

Studies (259)

Study Types

Clinical Trials (69)

Trial Overview

Trial Outcomes

Effect of Isosorbide Dinitrate on Central Venous Pressure

Effect of Isosorbide Dinitrate on Liver Stiffness Levels

Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Heart Rate Response

Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Respiratory Rate Response

Effect of Isosorbide Dinitrate on Maximal Exercise Capacity VO2 Max

Number of Participants Who Experience an Adverse Reaction to the Study Medication During the Study Enrollment Period.

Cesarean Delivery Rate

Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid

Forearm Blood Flow (FBF)

Net Glucose Uptake

Net Tissue-type Plasminogen Activator (t-PA) Release

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT)

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG)

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT)

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG)

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT)

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT)

Part II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state

Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours

Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study

Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes

Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment

Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours)

Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes

Percentage to First Achieve Initial Prespecified SBP Target Range [≥20 mm Hg and ≤40 mm Hg Apart] and 15% Reduction From Baseline Within First 30 Minutes

SBP Area Under the Curve (AUC) Outside Prespecified Target Range

Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes

Time to Use Other IV Antihypertensives During the Study Drug Administration

Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point

Early Diastolic Mitral Annular Velocity

LV Mass

Myocardial Extracellular Volume Fraction

Quality of Life (Kansas City Cardiomyopathy Questionnaire Score)

Wave Reflection Magnitude

Cardiovascular Hospitalization

Carotic Atherosclerotic Lesions

Coronary Artery Bypass [Coronary Revascularization]

Diameter of Stenosis [Carotic Atherosclerotic Lesions]

Level of Insulin Resistance 1

Level of Insulin Resistance 2

Lipid Metabolism 1

Lipid Metabolism 2

Lipid Metabolism 3

Percutaneous Coronary Intervention [Coronary Revascularization]

Safety and Tolerability 1

Safety and Tolerability 2

Safety and Tolerability 3

Safety and Tolerability 4

Systemic Inflammation Level

Thickness of the Intima-media Complex

Сardiovascular Death

Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg + ISMN 60 mg Versus Single Dose of Placebo

Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg Plus ISMN 60 mg Versus Single Dose of Losartan 100 mg

Arbitrary Accelerometry Units (AAU) (Phase I)

Arbitrary Accelerometry Units (AAU) (Phase II)

Borg Score During 6 Minute Walk Test (Phase I)

Borg Score During 6 Minute Walk Test (Phase II)

Improvement in Daily Activity - Area Under the Curve (Phase I)

Improvement in Daily Activity - Area Under the Curve (Phase II)

Improvement in Daily Activity - Hours Active Per Day (Phase I)

Improvement in Daily Activity - Hours Active Per Day (Phase II)

Improvement in Daily Activity - Slope of Daily Average (Phase I)

Improvement in Daily Activity - Slope of Daily Average (Phase II)

Kansas City Cardiomyopathy Questionnaire Overall Summary Score (Phase I)