A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of IV Infusion Treatment With Omecamtiv Mecarbil in Subjects With Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure
- Conditions
- Acute heart failureMedDRA version: 13.1Level: LLTClassification code 10000803Term: Acute heart failureSystem Organ Class: 10007541 - Cardiac disorders
- Registration Number
- EUCTR2010-021003-24-GR
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
Subject or subject’s legally acceptable representative has provided informed consent.
Male or female = 18 years of age at the time of randomization.
Current hospitalization for a primary reason of worsening heart failure (determined by the investigator) and requiring IV therapy for heart failure.
History of chronic heart failure (defined as requiring treatment for heart failure for a minimum of 30 days before hospitalization).
History of left ventricular ejection fraction (LVEF) = 35% (echocardiogram, radionuclide ventriculography, cardiac magnetic resonance imaging, or contrast ventriculography) within 12 months before randomization and without a subsequent intervening value of > 35%.
Dyspnea at rest due to heart failure at least 2 hours after having received = 40 mg intravenous furosemide (or equivalent dose of an alternative loop diuretic) during the current hospitalization; dyspnea should be present at randomization.
Brain-type natriuretic peptide (BNP) = 400 pg/mL or NT-proBNP = 1600 pg/mL during screening (BNP = 600 pg/mL or NT-proBNP = 2400 pg/mL if the subject has atrial fibrillation at presentation).
Female subjects, if not postmenopausal or sterilized, must have a negative pregnancy test, must not be breastfeeding and must agree to abstain from sexual intercourse or use highly effective methods of birth control during treatment and for 5 days following the last dose of investigational product. Highly effective methods of birth control include: sterilization, birth control pills, Depo-Provera® injections, or contraceptive implants. Postmenopausal female is defined as 12 continuous months of spontaneous amenorrhea.
Male subjects with a partner of childbearing potential must agree to inform their partner of their participation in this clinical study and, during treatment and for 5 days after the last dose of investigational product, to abstain from sexual intercourse or use highly effective methods of birth control, such as: vasectomy or a condom in combination with hormonal birth control or barrier methods used by the woman. For male subjects with pregnant partners, sexual abstinence or a condom must be used for 5 days after the last dose.
If participating in the PK/PD substudy, subject must currently be in sinus rhythm.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Disease-specific
Receiving IV vasopressor (excluding dopamine = 5 µg/kg/min), inotropic or mechanical (eg, intra-aortic balloon pump counterpulsation) support between admission to the hospital and randomization.
Subject has a pulmonary artery catheter.
Subject requires endotracheal mechanical ventilation.
Subject has acute coronary syndrome.
Within 6 weeks prior to enrollment: cardiac resynchronization therapy (CRT) or implantable cardioverter defibrillator (ICD) implantation, hospitalization for acute coronary syndrome, coronary revascularization, transient ischemic attack or stroke, sustained ventricular arrhythmia, or major surgery.
Likely to receive within 6 months after randomization, in the opinion of the investigator, planned revascularization, implantation of ICD, or CRT, ventricular assist device, continuous inotropic therapy, intermittent out-patient inotropic therapy, hospice care, or cardiac transplant.
Severe aortic or mitral stenosis or heart failure primarily due to valvular heart disease or clinically significant valvular heart disease that might lead to surgical correction within 6 months of randomization.
Hypertrophic obstructive cardiomyopathy, active myocarditis, or constrictive pericarditis, or clinically significant congenital heart disease.
Chronic antiarrhythmic therapy, with the exception of amiodarone.
Routinely scheduled outpatient IV infusions for HF (eg, inotropes, vasodilators [eg, nesiritide], diuretics) or routinely scheduled ultrafiltration.
Evidence of digitalis intoxication.
Other medical conditions
Blood pressure (BP) > 160/100 mm Hg, systolic BP (SBP) < 90 mm Hg, or heart rate (HR) > 110 bpm or HR < 60 bpm at screening and confirmed by a repeat assessment.
Estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) equation < 30 mL/min/1.73m2 at screening.
Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 1 year.
Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal) or receiving renal replacement therapy by dialysis.
Receiving or has received chemotherapy and/or radiation therapy for treatment of a malignancy within 6 months prior to randomization or clinical evidence of current malignancy, with the following exceptions: localized basal or squamous cell carcinoma of the skin or cervical intraepithelial neoplasia.
Untreated hypothyroidism or hyperthyroidism, adrenal insufficiency, active vasculitis due to collagen vascular disease.
Hepatic impairment defined by a total bilirubin = 2 times the upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 5 times ULN at screening.
General or other
Previously received omecamtiv mecarbil.
Currently enrolled in another investigational heart failure device or drug study, or less than 30 days since ending another investigational heart failure device or drug study, or receiving other investigational agent(s) for heart failure.
Recent (within 3 months) history of alcohol or illicit drug abuse based on self-report.
Known sensitivity to any of the products to be administered during dosing.
Subject previously has entered this study.
Subject will not be available for protocol-required study visits, to the best of the subject’s or investigator’s knowledge.
Any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give writte
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method