Health Condition 1: null- Acute Myocardial Infarction Health Condition 2: I219- Acute myocardial infarction, unspecified
Conditions
Interventions
Intervention1: LCZ696. LCZ696
50mg, 100mg and 200
mg dosage strengths will
be available for dose
adjustments: LCZ696 at dose levels 1-3 (50, 100 and 200 mg twice daily).
LCZ696 50 mg b.i.d. at V101 f
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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 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.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the time-tofirst occurrence of CV death or HF hospitalizationTimepoint: 32 months;To demonstrate the superiority of LCZ696, compared to ramipril, in delaying the time to new onset of symptomatic HF defined as time-to-first occurrence of HF hospitalization or outpatient HFTimepoint: 32 months;To demonstrate the superiority of LCZ696 compared to ramipril, in delaying the time-tofirst 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 all-cause mortalityTimepoint: 32 months | — |
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 function and or pulmonary congestion following the AMITimepoint: 32 months | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Croatia, Czech Republic, Denmark, Finland, France, Germany, Greece, Guatemala, Hungary, India, Israel, Italy, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Portugal, Republic of Korea, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States of America
Contacts
Public ContactMurugananthan K
Novartis Healthcare Private Limited
Outcome results
None listed