Exercise Capacity Study of LCZ696 vs. Enalapril in Patients With Chronic Heart Failure and Reduced Ejection Fraction.

NCT ID: NCT02768298

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-12
• Study Completion Date: 2019-11-25

Brief Summary

The purpose of the study was to determine the effect of LCZ696 vs. enalapril on improvement of exercise capacity in patients with chronic heart failure with reduced ejection fraction.

Detailed Description

This study was a randomized, double-blind, double-dummy, parallel-group, active-controlled, two-arm trial to compare LCZ696 200 mg twice daily (bid) to enalapril 10 mg bid in improving exercise capacity, daily physical activity and quality of life in patients with stable chronic heart failure (New York Heart Association III) and reduced left ventricular ejection fraction (LVEF ≤ 40%).

The study consisted of a screening period of 2 weeks during which the subject's eligibility for the study was assessed followed by a double blind treatment period of 12 weeks. Eligible subjects were randomized 1:1 to receive either LCZ696 or enalapril during the double-blind period. Treatment was initiated with LCZ696 100 mg bid or enalapril 5 mg bid (enalapril 10 mg bid for patients at a stable daily dose of enalapril above 10 mg per day or corresponding doses of other angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) prior first screening visit), respectively. Dose was up-titrated after 2 weeks to the final dose of LCZ696 200 mg bid or enalapril 10 mg bid.

Patients continued to take their background medications for chronic heart failure during the study, with the exception of ACEI or ARBs which were replaced by investigational treatment and had to be discontinued before first dose of study drug.

The primary objective was to demonstrate the superiority of LCZ696 200 mg bid compared to enalapril 10 mg bid in improving exercise tolerance (peak respiratory oxygen uptake (VO2peak), adjusted to body weight) as assessed by cardio-pulmonary-exercise testing (CPET) in patients with stable chronic heart failure (NYHA III) and reduced ejection fraction (LVEF ≤ 40%) after 3 months treatment.

Conditions

Chronic Heart Failure With Reduced Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

LCZ696

LCZ696 100 mg oral twice daily (bid) for 2 weeks followed by LCZ696 200 mg oral bid for 10 weeks.

Group Type: EXPERIMENTAL

LCZ696

Intervention Type: DRUG

LCZ696 100 mg bid for 2 weeks followed by LCZ696 200 mg bid for 10 weeks. Treatment was administered as oral tablets.

Placebo matching enalapril

Intervention Type: DRUG

Patients randomized to LCZ696 arm also received placebo matching enalapril (enalapril 0 mg tablets) to ensure the blinding during the entire course of the study.

Enalapril

Enalapril 5 mg oral twice daily (bid) for 2 weeks followed by enalapril 10 mg oral bid for 10 weeks.

Patients who prior Screening were at a stable daily dose of enalapril above 10 mg per day (or corresponding doses of other ACEI/ARB) started the study at a dose of enalapril 10 mg bid.

Group Type: ACTIVE_COMPARATOR

Enalapril

Intervention Type: DRUG

Enalapril 5 mg bid for 2 weeks followed by enalapril 10 mg bid for 10 weeks. Treatment was administered as oral tablets.

Patients who prior Screening were at a stable daily dose of enalapril above 10 mg per day (or corresponding doses of other ACEI/ARB) started the study at a dose of enalapril 10 mg bid.

Placebo matching LCZ696

Intervention Type: DRUG

Patients randomized to enalapril arm also received placebo matching LCZ696 (LCZ696 0 mg tablets) to ensure the blinding during the entire course of the study.

Interventions

LCZ696

LCZ696 100 mg bid for 2 weeks followed by LCZ696 200 mg bid for 10 weeks. Treatment was administered as oral tablets.

Intervention Type: DRUG

Enalapril

Enalapril 5 mg bid for 2 weeks followed by enalapril 10 mg bid for 10 weeks. Treatment was administered as oral tablets.

Patients who prior Screening were at a stable daily dose of enalapril above 10 mg per day (or corresponding doses of other ACEI/ARB) started the study at a dose of enalapril 10 mg bid.

Intervention Type: DRUG

Placebo matching enalapril

Patients randomized to LCZ696 arm also received placebo matching enalapril (enalapril 0 mg tablets) to ensure the blinding during the entire course of the study.

Intervention Type: DRUG

Placebo matching LCZ696

Patients randomized to enalapril arm also received placebo matching LCZ696 (LCZ696 0 mg tablets) to ensure the blinding during the entire course of the study.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with a diagnosis of chronic heart failure (NYHA class III) and reduced ejection fraction (LVEF ≤ 40%)
• Reduced ability to exercise, evidenced by VO2peak ≤ 18 ml/min per kg
• Patients had to 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 prior to the screening visit and until randomization visit.

Exclusion Criteria

• 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
• Impaired renal function
• Pregnant or nursing (lactating) women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Regensburg, Bavaria, Germany

Novartis Investigative Site

Dresden, Saxony, Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Bonn, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Dresden, , Germany

Novartis Investigative Site

Dresden, , Germany

Novartis Investigative Site

Erfurt, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Freiburg im Breisgau, , Germany

Novartis Investigative Site

Göttingen, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Koblenz, , Germany

Novartis Investigative Site

Koeln-Nippes, , Germany

Novartis Investigative Site

Leverkusen, , Germany

Novartis Investigative Site

Ludwigsburg, , Germany

Novartis Investigative Site

Ludwigshafen, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Neuwied, , Germany

Novartis Investigative Site

Nienburg, , Germany

Novartis Investigative Site

Rotenburg an der Fulda, , Germany

Novartis Investigative Site

Rüdersdorf, , Germany

Novartis Investigative Site

Siegen, , Germany

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Villingen-Schwenningen, , Germany

Novartis Investigative Site

Worms, , Germany

Novartis Investigative Site

Wuppertal, , Germany

Novartis Investigative Site

Würzburg, , Germany

Countries

Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=647

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

2015-004632-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLCZ696BDE01

Identifier Type: -

Identifier Source: org_study_id