A multi-center, randomized, double-blind, active-controlled, parallelgroup Phase 3 study to evaluate the efficacy and safety of LCZ696 compared to ramipril on morbidity and mortality in high risk<br>patients following an acute myocardial infarctio
- Conditions
- Heart attack10028593
- Registration Number
- NL-OMON47687
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 250
- 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 <60 mL/min/1.73 m2 based on Modification of Diet in Renal Disease (MDRD)
formula at screening visit
* Type I or II diabetes mellitus
* Documented history of prior MI
* Atrial fibrillation as noted by ECG, associated with index MI
* LVEF < 30% associated with index MI
* Worst Killip class III or IV associated with index MI requiring intravenous
treatment
* STEMI without reperfusion therapy within the first 24 hours after presentation
- Hemodynamically stable defined as:
* SBP * 100 mmHg at randomization for patients who received ACEi/ARB during the
last 24 hours prior to randomization
* SBP * 110 mmHg at randomization for patients who did not receive ACEi/ARB
during the last 24 hours prior to randomization
* No intravenous treatment with diuretics, vasodilators, vasopressors and/or
inotropes during the last 24 hours prior to randomization
Other protocol-defined inclusion criteria may apply.
- 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 < 30 ml/min/1.73 m2 as measured by the Modification of Diet in Renal
Disease (MDRD) formula at screening
- Serum potassium > 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method