Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event

Study Overview
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Brief Summary
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To explore two modalities of treatment initiation (Pre-discharge, and Post-discharge) with LCZ696 in HFrEF patients following stabilization after an ADHF episode.

Official Title
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A Multicenter, Randomized, Open Label, Parallel Group Study Comparing Pre-discharge and posT-discharge tReatment Initiation With LCZ696 in heArt Failure patieNtS With Reduced ejectIon-fracTion hospItalized for an Acute decOmpensation eveNt (ADHF)

Conditions
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Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
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* Drug: LCZ696


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients hospitalized due to acute decompensated HF episode (ADHF) as primary diagnosis) and consistent Signs & Symptoms Diagnosis of HF New York Heart Association class II-to-IV and reduced ejection fraction: Left ventricular ejection fraction ≤ 40% at Screening Patients did not receive any IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for ADHF to Randomization Stabilized (while in the hospital) for at least 24 hours leading to Randomization. Meeting one of the following criteria: Patients on any dose of ACEI or ARB at screening ACEI/ARB naïve patients and patients not on ACEI or ARB for at least 4 weeks before screening. Exclusion Criteria: History of hypersensitivity to the sacubitril, valsartan, or any ARBs, NEP inhibitors or to any of the LCZ696 excipients. Symptomatic hypotension and/or a SBP below 110 mm Hg or SBP above 180 mm Hg prior to randomization End stage renal disease at Screening; or estimated GFR below 30 mL/min/1.73 m2 (as measured by MDRD formula at Randomization. Serum potassium above 5.4 mmol/L at Randomization. Known history of hereditary or idiopathic angioedema or angioedema related to previous ACE inhibitor or ARB therapy Severe hepatic impairment, biliary cirrhosis and cholestasis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pre-discharge treatment initiation<br>Patients received first dose at any point after Randomization but no later than 12 h before discharge. | Drug: LCZ696<br>* LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food. The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.<br>|
| Other: Post-discharge treatment initiation<br>Patients received first dose after discharge and up to 14 days thereafter. | Drug: LCZ696<br>* LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food. The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving the Target Dose of LCZ696 200 mg Bid at 10 Weeks Post Randomization | Percentage of patients achieving and maintaining LCZ696 200 mg bid for at least 2 weeks leading to Week 10 | 10 weeks after Randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving and Maintaining Either LCZ696 100 mg and/or 200 mg Bid | Percentage of patients achieving and maintaining either LCZ696 100 mg and/or 200 mg bid for at least 2 weeks leading to Week 10 | 10 weeks after Randomization | 
| Percentage of Patients Achieving and Maintaining Any Dose of LCZ696 | Percentage of patients achieving any dose of LCZ696 for at least 2 weeks leading to 10 weeks of treatment | 10 weeks after Randomization | 
| Percentage of Patients Permanently Discontinued From Treatment | Percentage of patients permanently discontinued from LCZ696 (1) up to week 10 due to AEs, and (2) up to week 26 due to any reasons | 10 weeks after Randomization AND 26 weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute decompensated heart failure, Pre-discharge treatment, Post-discharge treatment, Angiotensin receptor neprilysine inhibitor, HFrEF, Reduced ejection fraction