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

Phase 3

Completed

• Conditions: Chronic Heart Failure With Reduced Ejection Fraction
• Interventions: Drug: LCZ696

• Registration Number: NCT02226120
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-08-25
• Study First Submitted QC: 2014-08-25
• Study First Posted: 2014-08-27
• Study Start: 2014-10-16
• Primary Completion: 2017-12-28
• Study Completion: 2017-12-28
• Results First Submitted: 2018-12-18
• Status Verified: 2019-02
• Results First Submitted QC: 2019-02-19
• Last Update Submitted: 2019-02-19
• Results First Posted: 2019-02-20
• Last Update Posted: 2019-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1980

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LCZ696	LCZ696	Angiotensin receptor antagonist neprilysin inhibitor (ARNI) with target dose of 200 mg bid

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability of LCZ696	From first dose of study treatment to 30 days after last dose of study treatment, up to 30 months.	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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Worcester, United Kingdom