Page last updated: 2024-10-21

urea and Ventricular Dysfunction, Left

urea has been researched along with Ventricular Dysfunction, Left in 30 studies

pseudourea: clinical use; structure
isourea : A carboximidic acid that is the imidic acid tautomer of urea, H2NC(=NH)OH, and its hydrocarbyl derivatives.

Ventricular Dysfunction, Left: A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.

Research Excerpts

ExcerptRelevanceReference
"We previously conducted a prospective study of landiolol hydrochloride (INN landiolol), an ultrashort-acting β-blocker, and reported that it could prevent atrial fibrillation after cardiac surgery."9.20Safety and efficacy of landiolol hydrochloride for prevention of atrial fibrillation after cardiac surgery in patients with left ventricular dysfunction: Prevention of Atrial Fibrillation After Cardiac Surgery With Landiolol Hydrochloride for Left Ventric ( Arimoto, M; Hata, H; Ishii, Y; Osaka, S; Sezai, A; Shiono, M; Yaoita, H, 2015)
" The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction."9.17Urgent management of rapid heart rate in patients with atrial fibrillation/flutter and left ventricular dysfunction: comparison of the ultra-short-acting β1-selective blocker landiolol with digoxin (J-Land Study). ( Aiba, T; Atarashi, H; Daimon, T; Fujino, K; Hori, M; Ikeda, T; Imai, Y; Inoue, H; Kinugawa, K; Kitakaze, M; Nagai, R; Nagano, T; Okamura, T; Sakamoto, A; Seino, Y; Shimizu, W; Yamashita, T, 2013)
"Omecamtiv mecarbil improved cardiac function in patients with heart failure caused by left ventricular dysfunction and could be the first in class of a new therapeutic agent."9.15The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. ( Clarke, CP; Cleland, JG; Francis, DP; Goldman, JH; Greenberg, BH; Lang, CC; Lee, JH; Malik, FI; Mayet, J; Mc Murray, JJ; Monaghan, M; Neyses, L; Nifontov, EM; Saikali, KG; Saltzberg, M; Senior, R; Shaburishvili, T; Teerlink, JR; Tsyrlin, VA; Wasserman, SM; Wolff, AA, 2011)
"Clinical experience with landiolol use in patients with atrial fibrillation (AF) and a severely depressed left ventricular (LV) function is limited."7.96Comparison of Landiolol and Digoxin as an Intravenous Drug for Controlling the Heart Rate in Patients with Atrial Fibrillation and Severely Depressed Left Ventricular Function. ( Akitsu, K; Fujino, T; Ikeda, T; Kinoshita, T; Koike, H; Shinohara, M; Suzuki, T; Wada, R; Yano, K, 2020)
"The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia."7.78Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure. ( Doi, M; Fukuta, S; Kobayashi, S; Matsuzaki, M; Murakami, W; Nao, T; Okamura, T; Okuda, S; Susa, T; Tanaka, T; Wada, Y; Yamada, J; Yano, M, 2012)
"To specifically assess the synthetic activity of the L-arginine-NO metabolic pathway, urinary excretion of [15N]nitrates and [15N]urea was determined after a primed continuous intravenous infusion of L-[15N]arginine (40 micromol/kg) in 16 patients with congestive heart failure and 9 age-matched normal control subjects at rest and during submaximal treadmill exercise."7.70Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure. ( Katz, SD; Khan, T; Knecht, M; Mathew, L; Potharlanka, P; Whelan, J; Zeballos, GA, 1999)
"Landiolol was ineffective in the majority of AFl/AT patients."5.51Differential Effectiveness of Landiolol Between Atrial Fibrillation and Atrial Flutter/Atrial Tachycardia Patients With Left Ventricular Dysfunction. ( Fujimoto, Y; Hayashi, H; Hayashi, M; Ito-Hagiwara, K; Iwasaki, YK; Maru, E; Oka, E; Shimizu, W; Yamamoto, T; Yodogawa, K, 2019)
"The patient was a 20-year old male with dilated cardiomyopathy."5.42An Experience of Landiolol Use for an Advanced Heart Failure Patient With Severe Hypotension. ( Amiya, E; Endo, M; Hatano, M; Imamura, T; Inaba, T; Kinugawa, K; Komuro, I; Maki, H; Nitta, D, 2015)
"Landiolol has a cardioprotective effect on I/R injury in the rat heart when administered before ischemia."5.34Pre-ischemic administration of landiolol prevents ischemia-reperfusion injury in the rat heart. ( Hirai, H; Minamiyama, Y; Sakaguchi, M; Sasaki, Y; Shibata, T; Suehiro, S; Takahashi, Y; Takemura, S, 2007)
"We previously conducted a prospective study of landiolol hydrochloride (INN landiolol), an ultrashort-acting β-blocker, and reported that it could prevent atrial fibrillation after cardiac surgery."5.20Safety and efficacy of landiolol hydrochloride for prevention of atrial fibrillation after cardiac surgery in patients with left ventricular dysfunction: Prevention of Atrial Fibrillation After Cardiac Surgery With Landiolol Hydrochloride for Left Ventric ( Arimoto, M; Hata, H; Ishii, Y; Osaka, S; Sezai, A; Shiono, M; Yaoita, H, 2015)
"Results from the multicenter trial (J-Land study) of landiolol versus digoxin in atrial fibrillation (AF) and atrial flutter (AFL) patients with left ventricular (LV) dysfunction revealed that landiolol was more effective for controlling rapid HR than digoxin."5.19Impacts of patient characteristics on the effectiveness of landiolol in AF/AFL patients complicated with LV dysfunction: Subgroup analysis of the J-Land study. ( Aiba, T; Atarashi, H; Daimon, T; Fujino, K; Hori, M; Ikeda, T; Imai, Y; Inoue, H; Kinugawa, K; Kitakaze, M; Nagai, R; Nagano, T; Okamura, T; Sakamoto, A; Seino, Y; Shimizu, W; Yamashita, T, 2014)
" The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction."5.17Urgent management of rapid heart rate in patients with atrial fibrillation/flutter and left ventricular dysfunction: comparison of the ultra-short-acting β1-selective blocker landiolol with digoxin (J-Land Study). ( Aiba, T; Atarashi, H; Daimon, T; Fujino, K; Hori, M; Ikeda, T; Imai, Y; Inoue, H; Kinugawa, K; Kitakaze, M; Nagai, R; Nagano, T; Okamura, T; Sakamoto, A; Seino, Y; Shimizu, W; Yamashita, T, 2013)
"Omecamtiv mecarbil improved cardiac function in patients with heart failure caused by left ventricular dysfunction and could be the first in class of a new therapeutic agent."5.15The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. ( Clarke, CP; Cleland, JG; Francis, DP; Goldman, JH; Greenberg, BH; Lang, CC; Lee, JH; Malik, FI; Mayet, J; Mc Murray, JJ; Monaghan, M; Neyses, L; Nifontov, EM; Saikali, KG; Saltzberg, M; Senior, R; Shaburishvili, T; Teerlink, JR; Tsyrlin, VA; Wasserman, SM; Wolff, AA, 2011)
"Clinical experience with landiolol use in patients with atrial fibrillation (AF) and a severely depressed left ventricular (LV) function is limited."3.96Comparison of Landiolol and Digoxin as an Intravenous Drug for Controlling the Heart Rate in Patients with Atrial Fibrillation and Severely Depressed Left Ventricular Function. ( Akitsu, K; Fujino, T; Ikeda, T; Kinoshita, T; Koike, H; Shinohara, M; Suzuki, T; Wada, R; Yano, K, 2020)
"The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia."3.78Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure. ( Doi, M; Fukuta, S; Kobayashi, S; Matsuzaki, M; Murakami, W; Nao, T; Okamura, T; Okuda, S; Susa, T; Tanaka, T; Wada, Y; Yamada, J; Yano, M, 2012)
"To specifically assess the synthetic activity of the L-arginine-NO metabolic pathway, urinary excretion of [15N]nitrates and [15N]urea was determined after a primed continuous intravenous infusion of L-[15N]arginine (40 micromol/kg) in 16 patients with congestive heart failure and 9 age-matched normal control subjects at rest and during submaximal treadmill exercise."3.70Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure. ( Katz, SD; Khan, T; Knecht, M; Mathew, L; Potharlanka, P; Whelan, J; Zeballos, GA, 1999)
"Landiolol was ineffective in the majority of AFl/AT patients."1.51Differential Effectiveness of Landiolol Between Atrial Fibrillation and Atrial Flutter/Atrial Tachycardia Patients With Left Ventricular Dysfunction. ( Fujimoto, Y; Hayashi, H; Hayashi, M; Ito-Hagiwara, K; Iwasaki, YK; Maru, E; Oka, E; Shimizu, W; Yamamoto, T; Yodogawa, K, 2019)
"Omecamtiv mecarbil (OM) is a novel inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation."1.42Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity. ( Aasum, E; Bakkehaug, JP; Boardman, N; Engstad, ET; How, OJ; Kildal, AB; Larsen, TS; Myrmel, T; Næsheim, T; Rønning, L, 2015)
"The patient was a 20-year old male with dilated cardiomyopathy."1.42An Experience of Landiolol Use for an Advanced Heart Failure Patient With Severe Hypotension. ( Amiya, E; Endo, M; Hatano, M; Imamura, T; Inaba, T; Kinugawa, K; Komuro, I; Maki, H; Nitta, D, 2015)
"Landiolol has a cardioprotective effect on I/R injury in the rat heart when administered before ischemia."1.34Pre-ischemic administration of landiolol prevents ischemia-reperfusion injury in the rat heart. ( Hirai, H; Minamiyama, Y; Sakaguchi, M; Sasaki, Y; Shibata, T; Suehiro, S; Takahashi, Y; Takemura, S, 2007)
"Hemodialysis patients (n = 34) with ESRD were enrolled in a prospective manner."1.33Changes in B-type natriuretic peptide levels in hemodialysis and the effect of depressed left ventricular function. ( Awad, A; Boulware, M; McCullough, PA; Merhi, W; Mourad, I; Safley, DM; Sandberg, KR; Sullivan, RA, 2005)

Research

Studies (30)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's1 (3.33)18.2507
2000's3 (10.00)29.6817
2010's20 (66.67)24.3611
2020's6 (20.00)2.80

Authors

AuthorsStudies
Lewis, GD1
Voors, AA1
Cohen-Solal, A1
Metra, M1
Whellan, DJ1
Ezekowitz, JA1
Böhm, M2
Teerlink, JR5
Docherty, KF1
Lopes, RD1
Divanji, PH1
Heitner, SB1
Kupfer, S1
Malik, FI5
Meng, L1
Wohltman, A1
Felker, GM3
Crespo-Leiro, MG1
McDonagh, TA1
Barge-Caballero, E1
Shinohara, M1
Wada, R1
Yano, K1
Akitsu, K1
Koike, H1
Kinoshita, T1
Suzuki, T1
Fujino, T1
Ikeda, T3
Bernier, TD1
Buckley, LF1
Solomon, SD2
McMurray, JJV2
Cleland, JGF1
Abbasi, SA1
Zhang, H2
Globe, G1
Biering-Sørensen, T1
Minamisawa, M1
Claggett, B1
Liu, J1
Abbasi, S1
Kurtz, CE1
Syed, YY1
Oka, E2
Iwasaki, YK2
Maru, E1
Fujimoto, Y1
Ito-Hagiwara, K1
Hayashi, H1
Yamamoto, T1
Yodogawa, K1
Hayashi, M1
Shimizu, W4
Nitta, D2
Imamura, T2
Momomura, S1
Nagai, R2
Kinugawa, K3
Inoue, H2
Atarashi, H2
Seino, Y2
Yamashita, T2
Aiba, T2
Kitakaze, M2
Sakamoto, A2
Imai, Y2
Daimon, T2
Fujino, K2
Nagano, T2
Okamura, T3
Hori, M2
Zhou, J2
Cui, X1
Jin, X1
Tang, B1
Fu, M1
Herlitz, H1
Cui, J1
Zhu, H1
Sun, A1
Hu, K1
Ge, J1
Bakkehaug, JP2
Kildal, AB2
Engstad, ET2
Boardman, N2
Næsheim, T2
Rønning, L2
Aasum, E2
Larsen, TS2
Myrmel, T2
How, OJ2
Melby, SJ1
Sezai, A1
Osaka, S1
Yaoita, H1
Ishii, Y1
Arimoto, M1
Hata, H1
Shiono, M1
Endo, M1
Amiya, E1
Inaba, T1
Maki, H1
Hatano, M1
Komuro, I1
Kass, DA1
Linz, B1
Hohl, M1
Reil, JC1
Linz, D1
Takata, J1
Haruyama, N1
Arashi, T1
Mae, T1
Yousif, MH1
Benter, IF1
Roman, RJ1
Cleland, JG1
Senior, R1
Nifontov, EM1
Mc Murray, JJ1
Lang, CC1
Tsyrlin, VA1
Greenberg, BH1
Mayet, J1
Francis, DP1
Shaburishvili, T1
Monaghan, M1
Saltzberg, M1
Neyses, L1
Wasserman, SM1
Lee, JH1
Saikali, KG1
Clarke, CP1
Goldman, JH1
Wolff, AA1
Kobayashi, S1
Susa, T1
Tanaka, T1
Murakami, W1
Fukuta, S1
Okuda, S1
Doi, M1
Wada, Y1
Nao, T1
Yamada, J1
Yano, M1
Matsuzaki, M1
Yasumura, Y1
Ito, N1
Tashiro, T1
Morishige, N1
Nishimi, M1
Hayashida, Y1
Minematsu, N1
Kuwahara, G1
Sukehiro, Y1
Teratani, H1
Safley, DM1
Awad, A1
Sullivan, RA1
Sandberg, KR1
Mourad, I1
Boulware, M1
Merhi, W1
McCullough, PA1
Takahashi, Y1
Shibata, T1
Sasaki, Y1
Hirai, H1
Takemura, S1
Minamiyama, Y1
Sakaguchi, M1
Suehiro, S1
Katz, SD1
Khan, T1
Zeballos, GA1
Mathew, L1
Potharlanka, P1
Knecht, M1
Whelan, J1

Clinical Trials (3)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure With Reduced Ejection Fraction and Decreased Exercise Tolerance[NCT03759392]Phase 3276 participants (Actual)Interventional2019-04-09Completed
A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose Escalation Study to Select and Evaluate an Oral Modified Release Formulation of Omecamtiv Mecarbil in Subjects With Heart Failure and Left Ventricular Systolic Dysfunction[NCT01786512]Phase 2544 participants (Actual)Interventional2013-02-26Completed
A Phase II, Multi Center, Double-Blind, Randomized, Placebo Controlled, Dose-Escalation, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of CK-1827452 in Patients With Stable Heart Failure[NCT00624442]Phase 245 participants (Actual)Interventional2007-04-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20

The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study. (NCT03759392)
Timeframe: Baseline and Week 20

InterventionmL/min/kg (Least Squares Mean)
Omecamtiv Mecarbil-0.239
Placebo0.207

Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20

The effect of treatment on daily activity, as assessed by average daily activity units, was evaluated by actigraphy. Actigraphy was collected during 4 sessions throughout the study for 2 week intervals. (NCT03759392)
Timeframe: Baseline (Week -2 to Day 1) to Weeks 18-20

Intervention10^5 activity units (Least Squares Mean)
Omecamtiv Mecarbil-0.2
Placebo-0.5

Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20

Total workload was measured during CPET (cycle ergometry [preferred] or treadmill exercise testing) and represents the maximum load to which a participant was subjected during CPET in order to produce work. (NCT03759392)
Timeframe: Baseline and Week 20

InterventionWatt (Least Squares Mean)
Omecamtiv Mecarbil-3.798
Placebo1.590

Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20

Ventilatory efficiency (ventilation [VE]/volume of exhaled carbon dioxide [VCO2]) was measured through CPET with gas exchange analysis. (NCT03759392)
Timeframe: Baseline and Week 20

Interventionslope (Least Squares Mean)
Omecamtiv Mecarbil0.277
Placebo-0.138

Dose Escalation Phase: Area Under the Plasma Concentration-time Curve for a Dosing Interval of 12 Hours Post Dose (AUC12) for Omecamtiv Mecarbil

(NCT01786512)
Timeframe: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose

Interventionng*hr/mL (Mean)
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F12030
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F22000
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F21740
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F15070
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F25010
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F26550

Dose Escalation Phase: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)

(NCT01786512)
Timeframe: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.

Interventionng/mL (Mean)
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F1193
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F2201
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F2171
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F1492
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F2502
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F2601

Dose Escalation Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing on Day 7

(NCT01786512)
Timeframe: Day 7 at predose

Interventionng/mL (Mean)
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F1157
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F2137
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F2134
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F1376
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F2395
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F2476

Dose Escalation Phase: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)

(NCT01786512)
Timeframe: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.

Interventionhours (Mean)
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F13.9
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F22.0
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F24.2
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F12.6
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F22.2
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F24.6

Expansion Phase: Change From Baseline in Heart Rate at Week 20

Heart rate was measured using electrocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates. (NCT01786512)
Timeframe: Baseline and week 20

Interventionbpm (Least Squares Mean)
Expansion Phase: Placebo0.57
Expansion Phase: Omecamtiv Mecarbil 25 mg-0.77
Expansion Phase: OM PK-based Titration-2.40

Expansion Phase: Change From Baseline in Left Ventricular End Diastolic Diameter (LVEDD) at Week 20

LVEDD was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates. (NCT01786512)
Timeframe: Baseline and week 20

Interventioncm (Least Squares Mean)
Expansion Phase: Placebo0.089
Expansion Phase: Omecamtiv Mecarbil 25 mg0.023
Expansion Phase: OM PK-based Titration-0.040

Expansion Phase: Change From Baseline in Left Ventricular End Systolic Diameter (LVESD) at Week 20

LVESD was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates. (NCT01786512)
Timeframe: Baseline and week 20

Interventioncm (Least Squares Mean)
Expansion Phase: Placebo-0.242
Expansion Phase: Omecamtiv Mecarbil 25 mg-0.322
Expansion Phase: OM PK-based Titration-0.421

Expansion Phase: Change From Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) at Week 20

Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates. (NCT01786512)
Timeframe: Baseline and week 20

Interventionpg/mL (Least Squares Mean)
Expansion Phase: Placebo502
Expansion Phase: Omecamtiv Mecarbil 25 mg-319
Expansion Phase: OM PK-based Titration-468

Expansion Phase: Change From Baseline in Stroke Volume at Week 20

Stroke volume was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates. (NCT01786512)
Timeframe: Baseline and week 20

InterventionmL (Least Squares Mean)
Expansion Phase: Placebo-1.05
Expansion Phase: Omecamtiv Mecarbil 25 mg3.53
Expansion Phase: OM PK-based Titration2.58

Expansion Phase: Change From Baseline in Systolic Ejection Time (SET) at Week 20

Systolic ejection time was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates. (NCT01786512)
Timeframe: Baseline and week 20

Interventionseconds (Least Squares Mean)
Expansion Phase: Placebo0.0000
Expansion Phase: Omecamtiv Mecarbil 25 mg0.0112
Expansion Phase: OM PK-based Titration0.0250

Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events

"An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a preexisting medical condition. The event does not necessarily have a causal relationship with study treatment. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events.~Each adverse event was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, and Grade 4 = life-threatening AE.~A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria:~fatal~life threatening~required in-patient hospitalization or prolongation of existing hospitalization~resulted in persistent or significant disability/incapacity~congenital anomaly/birth defect~other medically important serious event" (NCT01786512)
Timeframe: From first dose of study drug to 4 weeks after last dose; treatment duration was 7 days in the dose escalation phase.

,,,,,,,
InterventionParticipants (Count of Participants)
Any treatment-emergent adverse event (TEAE)TEAE Grade ≥ 2TEAE Grade ≥ 3TEAE Grade ≥ 4Serious adverse eventsTEAE leading to discontinuation of study drugFatal adverse events
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F12100000
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F26110100
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F26100000
Dose-escalation Cohort 1: Placebo4000000
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F19520220
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F23100000
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F25110100
Dose-escalation Cohort 2: Placebo1100000

Expansion Phase: Maximum Observed Plasma Concentration of Omecamtiv Mecarbil

(NCT01786512)
Timeframe: Weeks 2 and 12 at predose and 1, 2, 4, 6, and 8 hours post-dose.

,
Interventionng/mL (Mean)
Week 2Week 12
Expansion Phase: OM PK-based Titration212318
Expansion Phase: Omecamtiv Mecarbil 25 mg212200

Expansion Phase: Number of Participants With Treatment-emergent Adverse Events

"An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a preexisting medical condition. The event does not necessarily have a causal relationship with study treatment. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events.~Each adverse event was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, and Grade 4 = life-threatening AE.~A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria:~fatal~life threatening~required in-patient hospitalization or prolongation of existing hospitalization~resulted in persistent or significant disability/incapacity~congenital anomaly/birth defect~other medically important serious event" (NCT01786512)
Timeframe: From first dose of study drug until 4 weeks after last dose; treatment duration was 20 weeks in the expansion phase.

,,
InterventionParticipants (Count of Participants)
Any treatment-emergent adverse event (TEAE)TEAE Grade ≥ 2TEAE Grade ≥ 3TEAE Grade ≥ 4Serious adverse eventsTEAEs leading to discontinuation of study drugFatal adverse events
Expansion Phase: OM PK-based Titration9561311132123
Expansion Phase: Omecamtiv Mecarbil 25 mg92602883681
Expansion Phase: Placebo916234530124

Expansion Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing

(NCT01786512)
Timeframe: Predose (before morning dose) at weeks 2, 8, 12, 16, and 20

,
Interventionng/mL (Mean)
Week 2Week 8Week 12Week 16Week 20
Expansion Phase: OM PK-based Titration179161263240239
Expansion Phase: Omecamtiv Mecarbil 25 mg174156165155149

CK-1827452 Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUClast)

Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion (NCT00624442)
Timeframe: 2 days

Interventionhour x nanogram/milliliter (Mean)
Cohort 1/2: 0.125 mg/kg/h + 0.0625 mg/kg/h1102.2
Cohort 1/2: 0.25 mg/kg/h + 0.125 mg/kg/h2314.3
Cohort 1/2: 0.5 mg/kg/h + 0.25 mg/kg/h4252.7
Cohort 1/2: 0.75 mg/kg/h + 0.375 mg/kg/h6060.7
Cohort 1/2: 1.0 mg/kg/h + 0.5 mg/kg/h8495.7
Cohort 3: 0.25 mg/kg/h + 0.025 mg/kg/h3982.7
Cohort 3: 0.5 mg/kg/h + 0.05 mg/kg/h8120.5
Cohort 3: 1.0 mg/kg/h + 0.1 mg/kg/h18450.7
Cohort 4: 0.25 mg.kg.h + 0.125 mg/kg/h + 0.025 mg/kg/h4399.0
Cohort 4: 0.5 mg/kg/h + 0.25 mg/kg/h + 0.05 mg/kg/h10624.8
Cohort 4: 1.0 mg/kg/h + 0.5 mg/kg/h + 0.1 mg/kg/h19394.3
Cohort 5: 1.0 mg/kg/h + 0.5 mg/kg/h + 0.1 mg/kg/h59044.6
Cohort 5: 0.75 mg/kg/h + 0.375 mg/kg/h + 0.075 mg/kg/h43605.5

CK-1827452 Maximum Observed Plasma Concentration (Cmax)

Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion (NCT00624442)
Timeframe: 2 days

Interventionnanogram/milliliter (Mean)
Cohort 1/2: 0.125 mg/kg/h + 0.0625 mg/kg/h96.1
Cohort 1/2: 0.25 mg/kg/h + 0.125 mg/kg/h195.0
Cohort 1/2: 0.5 mg/kg/h + 0.25 mg/kg/h347.1
Cohort 1/2: 0.75 mg/kg/h + 0.375 mg/kg/h558.1
Cohort 1/2: 1.0 mg/kg/h + 0.5 mg/kg/h635.9
Cohort 3: 0.25 mg/kg/h + 0.025 mg/kg/h165.3
Cohort 3: 0.5 mg/kg/h + 0.05 mg/kg/h279.9
Cohort 3: 1.0 mg/kg/h + 0.1 mg/kg/h633.0
Cohort 4: 0.25 mg.kg.h + 0.125 mg/kg/h + 0.025 mg/kg/h177.9
Cohort 4: 0.5 mg/kg/h + 0.25 mg/kg/h + 0.05 mg/kg/h403.3
Cohort 4: 1.0 mg/kg/h + 0.5 mg/kg/h + 0.1 mg/kg/h681.4
Cohort 5: 1.0 mg/kg/h + 0.5 mg/kg/h + 0.1 mg/kg/h884.5
Cohort 5: 0.75 mg/kg/h + 0.375 mg/kg/h + 0.075 mg/kg/h726.9

Change From Baseline of Fractional Shortening at Various CK-1827452 Plasma Concentrations

Pooled analysis of the echocardiographic measure fractional shortening from echocardiograms taken at all timepoints. Fractional shortening is the percentage of change from baseline in the left ventricular cavity dimension with systole. Echocardiograms from cohorts 1,2,3,4 and 5 (564 echocardiograms) were binned into either placebo group or 1 of 6 groups based on plasma concentration of CK-1827452. (NCT00624442)
Timeframe: 4 days

,,,,,
InterventionPercentage of change (Least Squares Mean)
# of Echocardiographic Observations (no units)Fractional Shortening Percent Change from Baseline
>0-100 ng/mL811
>100-200 ng/mL561
>200-300 ng/mL373
>300-400 ng/mL233
>400-500 ng/mL172
>500 ng/mL445

Change From Baseline of Systolic Ejection Time at Various CK-1827452 Plasma Concentrations

Pooled analysis of the echocardiographic measure systolic ejection time from echocardiograms taken at all timepoints. The systolic ejection time is the period during which the aortic valve is open and blood is flowing across the valve. Echocardiograms from cohorts 1,2,3,4 and 5 (564 echocardiograms) were binned into either placebo group or 1 of 6 groups based on plasma concentration of CK-1827452. (NCT00624442)
Timeframe: 4 days

,,,,,
Interventionmsec (Least Squares Mean)
# of Echocardiographic Observations (no units)Ejection Fraction msec Change from Baseline
>0-100 ng/mL841
>100-200 ng/mL6218
>200-300 ng/mL4247
>300-400 ng/mL2458
>400-500 ng/mL2059
>500 ng/mL4680

Reviews

2 reviews available for urea and Ventricular Dysfunction, Left

ArticleYear
Cardiac Myosin Activation for the Treatment of Systolic Heart Failure.
    Journal of cardiovascular pharmacology, 2021, 01-01, Volume: 77, Issue:1

    Topics: Animals; Cardiac Myosins; Cardiotonic Agents; Heart Failure, Systolic; Humans; Myocardium; Recovery

2021
Landiolol: A Review in Tachyarrhythmias.
    Drugs, 2018, Volume: 78, Issue:3

    Topics: Administration, Intravenous; Adrenergic beta-1 Receptor Antagonists; Atrial Fibrillation; Dose-Respo

2018

Trials

8 trials available for urea and Ventricular Dysfunction, Left

ArticleYear
Effect of Omecamtiv Mecarbil on Exercise Capacity in Chronic Heart Failure With Reduced Ejection Fraction: The METEORIC-HF Randomized Clinical Trial.
    JAMA, 2022, 07-19, Volume: 328, Issue:3

    Topics: Aged; Cardiovascular Agents; Chronic Disease; Double-Blind Method; Exercise Tolerance; Female; Heart

2022
Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure: Results From the COSMIC-HF Study.
    Circulation. Heart failure, 2020, Volume: 13, Issue:12

    Topics: Aged; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Patient Reporte

2020
Cardiac Myosin Activator Omecamtiv Mecarbil Improves Left Ventricular Myocardial Deformation in Chronic Heart Failure: The COSMIC-HF Trial.
    Circulation. Heart failure, 2020, Volume: 13, Issue:12

    Topics: Aged; Biomarkers; Double-Blind Method; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged;

2020
Urgent management of rapid heart rate in patients with atrial fibrillation/flutter and left ventricular dysfunction: comparison of the ultra-short-acting β1-selective blocker landiolol with digoxin (J-Land Study).
    Circulation journal : official journal of the Japanese Circulation Society, 2013, Volume: 77, Issue:4

    Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Flut

2013
Impacts of patient characteristics on the effectiveness of landiolol in AF/AFL patients complicated with LV dysfunction: Subgroup analysis of the J-Land study.
    Advances in therapy, 2014, Volume: 31, Issue:4

    Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Digoxin; Drug

2014
Safety and efficacy of landiolol hydrochloride for prevention of atrial fibrillation after cardiac surgery in patients with left ventricular dysfunction: Prevention of Atrial Fibrillation After Cardiac Surgery With Landiolol Hydrochloride for Left Ventric
    The Journal of thoracic and cardiovascular surgery, 2015, Volume: 150, Issue:4

    Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Surgical Procedures; F

2015
The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial.
    Lancet (London, England), 2011, Aug-20, Volume: 378, Issue:9792

    Topics: Blood Pressure; Cardiac Myosins; Cross-Over Studies; Double-Blind Method; Echocardiography; Female;

2011
Safety and efficacy of an ultrashort-acting β1-blocker on left ventricular dysfunction.
    The heart surgery forum, 2012, Volume: 15, Issue:4

    Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Artery Bypass; Do

2012

Other Studies

20 other studies available for urea and Ventricular Dysfunction, Left

ArticleYear
Omecamtiv mecarbil for patients with severe systolic dysfunction and hypotension.
    European heart journal, 2022, 12-21, Volume: 43, Issue:48

    Topics: Blood Pressure; Heart Failure; Humans; Hypotension; Stroke Volume; Urea; Ventricular Dysfunction, Le

2022
Comparison of Landiolol and Digoxin as an Intravenous Drug for Controlling the Heart Rate in Patients with Atrial Fibrillation and Severely Depressed Left Ventricular Function.
    International heart journal, 2020, Sep-29, Volume: 61, Issue:5

    Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; B

2020
Differential Effectiveness of Landiolol Between Atrial Fibrillation and Atrial Flutter/Atrial Tachycardia Patients With Left Ventricular Dysfunction.
    Circulation journal : official journal of the Japanese Circulation Society, 2019, 03-25, Volume: 83, Issue:4

    Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Humans; Male; Middle Aged; Morpho

2019
What Determines the Response to Landiolol?
    Circulation journal : official journal of the Japanese Circulation Society, 2019, 06-25, Volume: 83, Issue:7

    Topics: Atrial Fibrillation; Atrial Flutter; Humans; Morpholines; Tachycardia; Urea; Ventricular Dysfunction

2019
What Determines the Response to Landiolol? - Reply.
    Circulation journal : official journal of the Japanese Circulation Society, 2019, 06-25, Volume: 83, Issue:7

    Topics: Atrial Fibrillation; Atrial Flutter; Humans; Morpholines; Tachycardia; Urea; Ventricular Dysfunction

2019
Acute rate control in atrial fibrillation with left ventricular dysfunction.
    Circulation journal : official journal of the Japanese Circulation Society, 2013, Volume: 77, Issue:4

    Topics: Adrenergic beta-1 Receptor Antagonists; Anti-Arrhythmia Agents; Atrial Flutter; Digoxin; Female; Hea

2013
Association of renal biochemical parameters with left ventricular diastolic dysfunction in a community-based elderly population in China: a cross-sectional study.
    PloS one, 2014, Volume: 9, Issue:2

    Topics: Aged; China; Coronary Disease; Creatinine; Cross-Sectional Studies; Diastole; Echocardiography; Fema

2014
Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity.
    Circulation. Heart failure, 2015, Volume: 8, Issue:4

    Topics: Animals; Cardiotonic Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Metabo

2015
Might a beta blocker finally provide some relief from postoperative atrial fibrillation?
    The Journal of thoracic and cardiovascular surgery, 2015, Volume: 150, Issue:4

    Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Female; Humans; Male; Morpholines; Postoperative Compli

2015
An Experience of Landiolol Use for an Advanced Heart Failure Patient With Severe Hypotension.
    International heart journal, 2015, Volume: 56, Issue:5

    Topics: Adrenergic beta-1 Receptor Antagonists; Atrial Fibrillation; Biological Availability; Cardiomyopathy

2015
Letter by Teerlink et al Regarding Article, "Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity".
    Circulation. Heart failure, 2015, Volume: 8, Issue:6

    Topics: Animals; Cardiotonic Agents; Enzyme Activators; Female; Heart Failure; Male; Myocardial Infarction;

2015
Inhibition of NHE3-mediated Sodium Absorption in the Gut Reduced Cardiac End-organ Damage Without Deteriorating Renal Function in Obese Spontaneously Hypertensive Rats.
    Journal of cardiovascular pharmacology, 2016, Volume: 67, Issue:3

    Topics: Animals; Antihypertensive Agents; Blood Pressure; Disease Models, Animal; Genetic Predisposition to

2016
Response to Letter Regarding Article, "Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity".
    Circulation. Heart failure, 2015, Volume: 8, Issue:6

    Topics: Animals; Cardiotonic Agents; Enzyme Activators; Female; Heart Failure; Male; Myocardial Infarction;

2015
Alteration of fatal 1:1 conducted atrial flutter to less conducted ratio by landiolol infusion.
    Journal of anesthesia, 2016, Volume: 30, Issue:4

    Topics: Aged, 80 and over; Atrial Fibrillation; Atrial Flutter; Electrocardiography; Humans; Male; Morpholin

2016
Cytochrome P450 metabolites of arachidonic acid play a role in the enhanced cardiac dysfunction in diabetic rats following ischaemic reperfusion injury.
    Autonomic & autacoid pharmacology, 2009, Volume: 29, Issue:1-2

    Topics: 8,11,14-Eicosatrienoic Acid; Amidines; Animals; Arachidonic Acid; Blood Glucose; Body Weight; Corona

2009
Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure.
    Circulation journal : official journal of the Japanese Circulation Society, 2012, Volume: 76, Issue:7

    Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Aged; Arrhythmias, Cardiac; Cardiotonic Agents; C

2012
Combination of β-blocker and milrinone for acute heart failure.
    Circulation journal : official journal of the Japanese Circulation Society, 2012, Volume: 76, Issue:7

    Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiotonic Agents; Female; Heart Failure; Hemody

2012
Changes in B-type natriuretic peptide levels in hemodialysis and the effect of depressed left ventricular function.
    Advances in chronic kidney disease, 2005, Volume: 12, Issue:1

    Topics: Biomarkers; Blood Pressure; Dialysis Solutions; Echocardiography; Female; Fluorescence Polarization

2005
Pre-ischemic administration of landiolol prevents ischemia-reperfusion injury in the rat heart.
    Osaka city medical journal, 2007, Volume: 53, Issue:1

    Topics: Adrenergic beta-Antagonists; Animals; Dose-Response Relationship, Drug; Heart; Ischemic Precondition

2007
Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure.
    Circulation, 1999, Apr-27, Volume: 99, Issue:16

    Topics: Adult; Aged; Arginine; Cardiomyopathies; Creatinine; Exercise Test; Female; Heart Failure; Humans; L

1999