Open-label Extension Study for CLCZ696G2301 (PARADISE-MI)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to collect long-term safety and tolerability data of LCZ696 and to provide open-label LCZ696 to eligible participants who completed CLCZ696G2301 study (PARADISE-MI) if LCZ696 is shown to have a positive benefit-risk profile in comparison to ramipril in reducing risk of cardiovascular (CV) mortality and development of heart failure in participants enrolled in the PARADISE-MI study.

Official Title
-----------------
A Multicenter Study to Evaluate the Long-term Safety and Tolerability of Open-label LCZ696 in Patients With Acute Myocardial Infarction Who Previously Participated in CLCZ696G2301 (PARADISE-MI)

Conditions
-----------------
Post Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: sacubitril/valsartan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Participant received study treatment (either in LCZ696 or ramipril treatment arm) in PARADISE-MI. Participant is safe to be enrolled in the extension study and may benefit from the treatment of LCZ696 per investigator's clinical judgement. Exclusion Criteria: Participant with a known history of angioedema History of hypersensitivity to the study drug or drugs of similar chemical classes or known intolerance or contraindications to study drug or drugs of similar chemical classes including ACE inhibitors, ARB or NEP inhibitors Symptomatic hypotension at screening Serum potassium > 5.2 mmol /L (or equivalent plasma potassium value) at screening 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 Pregnant or nursing women or women of child-bearing potential unless they are using highly effective methods of contraception Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a multicenter, open-label extension study following-up to PARADISE-MI, which evaluated the efficacy and safety of LCZ696 compared to ramipril, in reducing the occurrence of CV death, heart failure (HF) hospitalization and outpatient HF (time-to-first event analysis) in post-acute myocardial infarction (AMI) patients with evidence of left ventricular (LV) systolic dysfunction and/or pulmonary congestion, without a known prior history of chronic HF. The study duration is up to approximately 24 months with visits at Days -14 to 1, 1, 15, 29 and Months 3, 6, 12, 18, and 24. Participants will receive LCZ696 at maximally tolerated doses with a target dose of 200 mg twice daily at all visits between day 1 and the last visit.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCZ696 (sacubitril/valsartan)<br>Following start of treatment, patients will receive LCZ696. Possible doses are level 1, 2, and 3 (50, 100 and 200 mg twice daily respectively) | Drug: sacubitril/valsartan<br>* LCZ696 (sacubitril/valsartan) tablet will be available in 24/26 mg, 49/51 mg and 97/103 mg, respectively<br>* Other names: LCZ696;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with AE(s) leading to permanent study drug discontinuation, temporary study drug interruption, or study drug dose adjustment will be reported and summarized | Adverse events (AEs) leading to treatment changes including treatment discontinuation, interruption, and dose adjustment | Up to 24 months | 
| Number of participants with Serious Adverse Events (SAEs) | SAE(s) will be reported, and the number of participants with SAE(s) will be summarized | Up to 24 months | 
| Vital signs (Blood Pressure and pulse) | BP and pulse will be measured at every visit. The test values of Systolic Blood Pressure (mmHg), Diastolic Blood Pressure (mmHg) and heart rate (rate/minute) as well as change from the baseline will be summarized by parameter, using number of observations, mean, standard deviation, median, minimum, and maximum | Baseline and up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LCZ696, Open-Label Extension, PARADISE-MI, Post Myocardial Infarction, Post Heart Attack, CLCZ696G2301