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

Novartis

Status and phase: Completed; Phase 3

Conditions: Chronic Heart Failure With Reduced Ejection Fraction

Treatments: Drug: LCZ696

Study type: Interventional

Funder types: Industry

Identifiers

NCT02226120

2014-001971-30 (EudraCT Number)

CLCZ696B2317

Details and patient eligibility

About

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.

Enrollment: 1,980 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Written informed consent for the extension must be obtained before any assessment is performed.
2. 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

1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
2. 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
3. Known history of angioedema
4. Requirement of simultaneous treatment with both ACEIs and ARBs
5. Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy)
6. Symptomatic hypotension and/or a SBP < 100 mmHg at Visit 1 (screening)
7. Estimated GFR < 30 mL/min/1.73m^2 as measured by the simplified MDRD formula at Visit 1 (screening)
8. Presence of bilateral renal artery stenosis
9. Serum potassium > 5.2 mmol/L at Visit 1 (screening)
10. 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
11. Pregnant or nursing (lactating) women
12. Women of child-bearing potential
13. 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1,980 participants in 1 patient group

LCZ696

Experimental group

Description:

Angiotensin receptor antagonist neprilysin inhibitor (ARNI) with target dose of 200 mg bid

Treatment:

Drug: LCZ696