None listed
Conditions
Interventions
Enalapril Type of group
There will be a titration phase of three levels starting from 2.5 mg BID.
The daily target dose is 20 mg, PO.
Duration: 14 months
Group name:Omapatrilat Type of group
There will be a titration phase of three levels starting from 10 mg QD. The daily target dose is 40 mg, PO. Duration: 14 months
Sponsors
BRISTOL MYERS SQUIBB PERÚ S.A.,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age>18years 2. Men or women. Women may not be pregnant or nursing. Women of child bearing potential (WOCBP) are eligible if they are practicing effective contraceptive measures. 3. Chronic heart failure of NYHA Functional Class II, III or IV in severity for at least 2 months. Subjects with no symptoms attributable to heart failure (Class I) are not eligible. 4. Hospitalization for worsening heart failure within the past 12 months. 5. The following medications are required, recommended or allowed at the time of enrolment into the study: Diuretics, ACE Inhibitors, Beta-blockers, Angiotensin II receptor blockers, Other Cardiac Therapies. 6. Willing and able to give informed consent. 7. Evidence by invasive or noninvasive cardiac imaging of left ventricular systolic dysfunction.
Exclusion criteria
Exclusion criteria: 1. Previous intolerance to ACE inhibitors, as indicated by a history of discontinuation of ACE-I due to urticaria, cough, bronchospasm, or angioedema. 2. Hemodynamically significant primary cardiac valvular disease, hypertrophic or restrictive cardiomyopathy, constrictive pericarditis, cor pulmonale or a history of myocarditis (including Chagas disease). 3. A heart transplant or left ventricular assist device or partial left ventricular resection (Batista procedure). 4. Unstable angina pectoris or myocardial infarction within 1 month or a coronary revascularization procedure (coronary artery bypass grafting or percutaneous transluminal angioplasty) within 3 months prior to enrolment. 5. Transient ischemia attack (TIA) or stroke within 3 months prior to enrolment. 6. Any of the following rhythm abnormalities: a. Second or third degree heart block or sick sinus syndrome (unless treated with a properly functioning pacemaker). b. History of resuscitated ventricular tachycardia, ventricular fibrillation or sudden death, unless (1) these occurred within 24 hours of an acute myocardial infarction; or (2) the subject has an implanted and properly functioning implantable cardioverter-defibrillator (ICD) which has not fired within 2 months prior to enrolment. 7. Any of the following medications within 2 weeks prior to enrollment: - Oral positive inotropic drugs (except digitalis) or - Lithium salts 8. Any of the following therapies: a. Intravenous therapy with a positive inotropic agent in an outpatient or short-stay unit within 2 weeks prior to enrollment. b. Therapy with omapatrilat (when approved for any indication) within 30 days of enrollment or prior history of intolerance to omapatrilat c. Treatment with an investigational drug within 30 days d. Participation in any other clinical trial of drug therapy until the present study has been terminated or completed. 9. Participation in an earlier trial with omapatrilat (regardless of treatment received) 10. Concomitant disorders that might compromise the ability to evaluate treatment or enhance the risks of therapy. 11. Any condition or disorder other than heart failure that: Requires ongoing hospitalization for treatment, or - may limit life expectancy within 3 years, or - would not permit optimal participation in the trial, or - would increase the risk of participation to the subject (in the opinion of the investigator)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Time to death (all cause) or fírst occurrence of hospitalization for worsening heart failure. A subject will be considered to have been hospitalized for heart failure if they were admitted to the hospital for the management of worsening heart failure (1) for a stay which included at least portions of 2 sequential calendar days and (2) received intravenous medication(s) for the treatment of heart failure on the calendar day of admission or on either of the 2 sequential calendar days The diagnosis of worsening heart failure will include (but not be restricted to) worsening signs and symptoms of heart failure, acute pulmonary edema, cardiogenic shock or peripheral hypoperfusion (and end-organ dysfunction). Measure:Efficacy Timepoints:Time to event | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Clinical evaluation Measure:Time to death due to any cause. Timepoints:Time to event ; Outcome name: Clinical evaluation Measure:Time to cardiovascular death and/or cardiovascular hospitalization. Timepoints: Time to event ; Outcome name:NYHA Functional Class at 8 months, with worst rank assigned for subjects who die, or who are hospitalized or discontinued for worsening heart failure. Measure:NYHA Functional Class Timepoints:8 months ; Outcome name:Time to combined ischemic endpoint: death myocardial infarction, hospitalization for unstable angina, or revascularization. Measure:Time to combined ischemic endpoint Timepoints:Time to event ; Outcome name:Patient global assessment at 8 months with worst rank assigned for subjects who die, or who are hospitalized or discontinued for worsening heart failure. Subject and physician global assessment, and subject assessment of dyspnea and fatigue will consist of a 7 point scale using the following categories: markedly improved, moderately improved, slightly improved, unchanged, slightly worsened, moderately worsened, and markedly worsened Measure:Patient global assessment Timepoints:8 months ; Outcome name:Frequency of significant changes in serum creatinine (1.5 X baseline and > 0.8 X upper limit of normal) and urea nitrogen (BUN; 2 X baseline and > upper limit of normal). Measure:Frequency of significant changes in serum creatinine and urea Timepoints:14 months | — |
Outcome results
None listed