This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure (PARADIGM-HF)

Novartis

Status and phase: Terminated; Phase 3

Conditions: Heart Failure With Reduced Ejection Fraction

Treatments: Drug: LCZ696 200 mg BID; Drug: Enalapril 10 mg BID

Study type: Interventional

Funder types: Industry

Identifiers

NCT01035255

2009-015834-31

CLCZ696B2314

Details and patient eligibility

About

The study will evaluate the efficacy and safety of LCZ696 compared to enalapril on morbidity and mortality in patients with chronic heart failure (NYHA Class II - IV and EF =< 35%).

Enrollment: 8,442 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must give written informed consent before any assessment is performed.
• Outpatients ≥ 18 years of age, male or female.
• Patients with a diagnosis of CHF NYHA class II-IV and reduced ejection fraction (EF =< 35%) and elevated BNP.
• Patients must be on an ACEI or an ARB at a stable dose of at least enalapril 10 mg/d or equivalent for at least 4 weeks.
• Patients must be treated with a β-blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks.

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 the study drugs.
• Previous history of intolerance to recommended target doses of ACEIs or ARBs
• Known history of angioedema.
• Requirement of 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.
• Estimated GFR < 30 mL/min/1.73m2 as measured by the simplified MDRD formula
• Serum potassium > 5.2 mmol/L.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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8,442 participants in 2 patient groups

LCZ696

Experimental group

Description:

single-blind active run-in period consisted of treatment with enalapril 10 mg bid, followed by LCZ696 100 mg bid, and then LCZ696 200 mg bid over a total duration of 5 to 10 weeks. Temporary down-titration from LCZ696 200 mg bid to LCZ696 100 mg bid was allowed provided the patient was up-titrated back to LCZ696 200 mg bid and tolerated this dose for at least two weeks before being eligible for randomization. LCZ696 200mg BID during double blind treatment period

Treatment:

Drug: LCZ696 200 mg BID

Enalapril

Active Comparator group

Description:

single-blind active run-in period consisted of treatment with enalapril 10 mg bid, followed by LCZ696 100 mg bid, and then LCZ696 200 mg bid over a total duration of 5 to 10 weeks. Temporary down-titration from LCZ696 200 mg bid to LCZ696 100 mg bid was allowed provided the patient was up-titrated back to LCZ696 200 mg bid and tolerated this dose for at least two weeks before being eligible for randomization. Enalapril 10 mg BID during double blind treatment period

Treatment:

Drug: Enalapril 10 mg BID