Safety and Tolerability During Open-label Treatment With LCZ696 in Patients With CHF and Reduced Ejection Fraction

Study Overview
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Brief Summary
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The purpose of this study was to collect safety and tolerability data on LCZ696 in eligible PARADIGM-HF patients who received open-label investigational drug. The parent PARADIGM-HF (NCT01035255) trial was terminated early due to compelling efficacy of LCZ696 in patients with heart failure with reduced ejection fraction (HFrEF) after the final pre-specified interim analysis in March 2014.

Official Title
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A Multicenter Study to Evaluate Safety and Tolerability in Patients With Chronic Heart Failure and Reduced Ejection Fraction From PARADIGM-HF Receiving Open Label LCZ696

Conditions
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Chronic 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: Written informed consent for the extension must be obtained before any assessment is performed. Patients who have completed PARADIGM-HF (protocol CLCZ696B2314) and are able to be safely enrolled into the open-label trial as judged by the investigator. Exclusion Criteria: Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to LCZ696 Known history of angioedema Requirement of simultaneous treatment with both ACEIs and ARBs Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy) Symptomatic hypotension and/or a SBP < 100 mmHg at Visit 1 (screening) Estimated GFR < 30 mL/min/1.73m^2 as measured by the simplified MDRD formula at Visit 1 (screening) Presence of bilateral renal artery stenosis Serum potassium > 5.2 mmol/L at Visit 1 (screening) Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 3 x ULN at Visit 1, history of hepatic encephalopathy, history of esophageal varices, or history of portacaval shunt Pregnant or nursing (lactating) women Women of child-bearing potential Any condition, not identified in the protocol, that in the opinion of the investigator is likely to prevent the patient from safely tolerating LCZ696 or complying with the requirements of the study.
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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCZ696<br>Angiotensin receptor antagonist neprilysin inhibitor (ARNI) with target dose of 200 mg bid | Drug: LCZ696<br>* Angiotensin receptor antagonist neprilysin inhibitor (ARNI) with target dose of 200 mg bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability of LCZ696 | The primary assessments for safety were the reporting of angioedema, AEs suspected to be related to LCZ696, AEs leading to study drug discontinuation and serious adverse events (SAE) including death. The assessment of safety were based primarily on the frequency of adverse events of special interest, sitting systolic and diastolic blood pressure, heart rate, and serious adverse events suspected by the investigators to be related to LCZ696 for the Safety set. Only descriptive analysis done. | From first dose of study treatment to 30 days after last dose of study treatment, up to 30 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LCZ696, chronic heart failure, ARNI, Congestive heart failure (CHF), heart failure (HF), acute heart failure syndrome, congestive cardiac failure (CCF)