Heart attack
Conditions
Interventions
Treatment with LCZ696 or Ramipril
Acute myocaridla infarction
Efficacy
LCZ696
Safety
Sponsors
Novartis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Male or female patients * 18 years of age. - Diagnosis of spontaneous AMI based on the universal myocardial infarction (MI) definition with randomization to occur between 12 hours and 7 days after index event presentation. - Evidence of LV systolic dysfunction and/or pulmonary congestion requiring intravenous treatment associated with the index MI event defined as: * LVEF * 40% after index MI presentation and prior to randomization and/or * Pulmonary congestion requiring intravenous treatment during the index hospitalization - At least one of the following 8 risk factors: * Age * 70 years * eGFR
Exclusion criteria
Exclusion criteria: - Known history of chronic HF prior to randomization - Cardiogenic shock within the last 24 hours prior to randomization - Persistent clinical HF at the time of randomization - Coronary artery bypass graft (CABG) performed or planned for index MI - Clinically significant right ventricular MI as index MI - Symptomatic hypotension at screening or randomization - Patients with a known history of angioedema - Stroke or transient ischemic attack within one month prior to randomization - Known or suspected bilateral renal artery stenosis - Clinically significant obstructive cardiomyopathy - Open-heart surgery performed within one month prior to randomization or planned cardiac surgery within the 3 months after randomization - eGFR 5.2 mmol /L (or equivalent plasma potassium value) at randomization - Known hepatic impairment (as evidenced by total bilirubin > 3.0 mg/dL or increased ammonia levels, if performed), or history of cirrhosis with evidence of portal hypertension such as esophageal varices - Previous use of LCZ696 or Entresto - Use of other investigational drugs within 30 days prior to screening - History of hypersensitivity to the study drugs or drugs of similar chemical classes - Known intolerance or contraindications to study drugs or drugs of similar chemical classes including ACE inhibitors, ARB or NEP inhibitors - Patients taking medications prohibited by the protocol that cannot be discontinued for the duration of the study - History of malignancy of any organ system (other than localized basal cell carcinoma of the skin) within the past 3 years with a life expectancy of less than 1 year - Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or extraction of study drug at investigators* discretion - History or evidence of drug or alcohol abuse within the last 12 months - Patients considered unsuitable for the study, including patients with psychiatric, behavioral or cognitive disorders, sufficient to interfere with the patient*s ability to understand and comply with the protocol instructions or follow-up procedures - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate that LCZ696 is superior to ramipril in delaying the timeto- first occurrence of the composite endpoint of CV death, HF hospitalization or outpatient HF* in patients with LV systolic dysfunction and/or pulmonary congestion following an AMI. (*The outpatient HF endpoint event is defined as an adjudicated event of clinical development of symptomatic HF (either urgent/unscheduled or non-urgent) in the outpatient setting with symptoms and signs requiring initiation/intensification of intravenous or qualifying oral HF treatment.) | — |
Secondary
| Measure | Time frame |
|---|---|
| - To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the time-to-first occurrence of CV death or HF hospitalization - To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the new onset of symptomatic HF defined as time-to-first occurrence of HF hospitalization or outpatient HF - To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the time-to-first occurrence of CV death, non-fatal spontaneous MI or non-fatal stroke - To demonstrate the superiority of LCZ696, compared to ramipril, in reducing the rate of the composite endpoint of CV death and total (first and recurrent) hospitalizations due to HF, non-fatal spontaneous MI or non-fatal stroke - To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the time to all-cause mortality - To evaluate the safety and tolerability of LCZ696 compared to ramipril | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Croatia, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Korea (the Democratic Peoples Republic of), Korea (the Republic of), Mexico, Netherlands, Norway, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan (Province of China), Thailand, Turkey, United Kingdom, United States of America
Outcome results
None listed