Study is to evaluate the efficacy and safety ofLCZ696 compared to ramipril when added to standard therapy, in reducing the occurrence ofcardiovascular (CV) death, heart failure (HF) hospitalization andoutpatient HF (time-to-first event analysis)
- Conditions
- Health Condition 1: null- Acute Myocardial InfarctionHealth Condition 2: I219- Acute myocardial infarction, unspecified
- Registration Number
- CTRI/2017/06/008867
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
Written informed consent must be obtained before any assessment is performed.
Male or female patients greater than equal to 18 years of age.
At least one of the following 8 risk factors:
Age greater than equal to 70 years
eGFR less than 60 mL per min per1.73 m2 based on MDRD formula at screening visit
Type I or II diabetes mellitus
Documented history of prior MI supported by ECG changes and or elevation of
cardiac enzymes consistent with MI diagnosis.
Atrial fibrillation as noted by ECG, associated with index MI
LVEF less than 30percent 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 greater than equal to 100 mmHg at randomization for patients who received ACE inhibitor or ARB during the last 24 hours prior to randomization (ACE inhibitor/ARB Yes patients)
SBP greater than equal to 110 mmHg at randomization for patients who did not receive ACE inhibitor/ARB during the last 24 hours prior to randomization (ACE inhibitor/ARB No patients)
No intravenous treatment with diuretics, vasodilators, vasopressors and/or inotropes
during the last 24 hours prior to randomization.
Evidence of LV systolic dysfunction and/or pulmonary congestion requiring intravenous
treatment associated with the index MI event defined as:
LVEF less than equal to 40percent assessed locally by echocardiography, magnetic resonance imaging, cardiac CT, radionuclide or contrast ventriculography after index MI presentation and prior to randomization.
(These examinations may be performed as part of patient standard-of-care. In case multiple LVEF measurements have been performed during index event, the last one performed prior to randomization should be considered as the qualifying measurement), and/or
- Pulmonary congestion requiring intravenous treatment during the index hospitalization
supported by clinical assessment (worst Killip class, II or above; see Appendix 3 for
Killip class definition) or radiological findings. Radiological evidence of pulmonary
congestion is defined as pulmonary venous congestion with interstitial or alveolar
edema and must be supported by at least one chest X-ray or CT scan.
1. Known history of chronic HF prior to randomization
2. Cardiogenic shock within the last 24 hours prior to randomization
3. Persistent clinical HF at the time of randomization
4. Coronary artery bypass graft (CABG) performed or planned for index MI.
5. Clinically significant right ventricular MI as index MI
6. Symptomatic hypotension at screening or randomization
7. Patients with a known history of angioedema
8. Stroke or transient ischemic attack within one month prior to
randomization
9. Known or suspected bilateral renal artery stenosis
10. Clinically significant obstructive cardiomyopathy
11. Open-heart surgery performed within one month prior to
randomization or planned cardiac surgery within the 3 months after
randomization
12. eGFR < 30 ml/min/1.73 m2 as measured by the Modification of Diet in
Renal Disease (MDRD) formula at screening
13. Serum potassium > 5.2 mmol /L at screening
14. 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 varices
15. Previous use of LCZ696 or EntrestoTM
16. Use of other investigational drugs within 30 days prior to screening
17. History of hypersensitivity to the study drugs or drugs of similar
chemical classes
18. Known intolerance or contraindications to study drugs or drugs of
similar chemical classes including ACE inhibitors, ARB or NEP
inhibitors
19. Patients taking medications prohibited by the protocol that cannot be
discontinued for the duration of the study
20. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 function and or pulmonary congestion following the AMITimepoint: 32 months
- Secondary Outcome Measures
Name Time Method To demonstrate the superiority of LCZ696 compared to ramipril, in delaying the time-tofirst <br/ ><br>occurrence of CV death, non-fatal spontaneous MI or non-fatal strokeTimepoint: 32 months;To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the time to <br/ ><br>all-cause mortalityTimepoint: 32 months;To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the time to <br/ ><br>new onset of symptomatic HF defined as time-to-first occurrence of HF hospitalization or <br/ ><br>outpatient HFTimepoint: 32 months;To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the time-tofirst <br/ ><br>occurrence of CV death or HF hospitalizationTimepoint: 32 months