Exercise Capacity Study of LCZ696 vs. Enalapril in Patients With Chronic Heart Failure and Reduced Ejection Fraction.
A Randomized, Double-blind, Active-controlled Study to Assess the Effect of LCZ696 Compared With Enalapril to Improve Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF).
2 other identifiers
interventional
201
1 country
34
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jul 2016
Typical duration for phase_4
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 9, 2016
CompletedFirst Posted
Study publicly available on registry
May 11, 2016
CompletedStudy Start
First participant enrolled
July 12, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 25, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 25, 2019
CompletedResults Posted
Study results publicly available
October 9, 2020
CompletedOctober 8, 2021
October 1, 2021
3.4 years
May 9, 2016
September 16, 2020
October 7, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Peak Respiratory Oxygen Uptake (VO2peak) Adjusted to Body Weight) After 3 Months of Treatment
Cardiopulmonary exercise testing (CPET) is an established method to evaluate the exercise tolerance of heart failure patients by evaluating the cardio-pulmonary system using the measurement of respiratory gases during physical (exercise) stress. One of the parameters attained by this test is the peak respiratory oxygen uptake (VO2peak). CPET to assess VO2peak was performed at a cycle ergometer at baseline (Visit 2, 9 days prior randomization) and after 6 weeks and 3 months of treatment (Visit 6 and Visit 7, respectively). The VO2peak adjusted to body weight was calculated based on the corresponding visit's VO2peak (unadjusted) and body weight data by using the following formula: VO2peak (unadjusted)/body weight. Higher values of VO2peak indicate less symptom severity and therefore a positive change from baseline indicates improvement.
Baseline, 3 months
Secondary Outcomes (4)
Change From Baseline in Peak Respiratory Oxygen Uptake (VO2peak) Adjusted to Body Weight) After 6 Weeks of Treatment
Baseline, 6 weeks
Change From Baseline in the Minute Ventilation (VE) to Carbon Dioxide Output Slope (VE/VCO2 Slope)
Baseline, 6 weeks, 3 months
Change From Baseline in Exercise Capacity (Watt) at Ventilatory Anaerobic Threshold (VAT)
Baseline, 6 weeks, 3 months
Change From Baseline in Rate of Perceived Exertion (Perceived Dyspnea and Perceived Fatigue) During Exercise Assessed by Borg Scale
Baseline, 3 months
Study Arms (2)
LCZ696
EXPERIMENTALLCZ696 100 mg oral twice daily (bid) for 2 weeks followed by LCZ696 200 mg oral bid for 10 weeks.
Enalapril
ACTIVE COMPARATOREnalapril 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.
Interventions
LCZ696 100 mg bid for 2 weeks followed by LCZ696 200 mg bid for 10 weeks. Treatment was administered as oral tablets.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (34)
Novartis Investigative Site
Regensburg, Bavaria, 93053, Germany
Novartis Investigative Site
Dresden, Saxony, 01099, Germany
Novartis Investigative Site
Berlin, 10787, Germany
Novartis Investigative Site
Berlin, 13055, Germany
Novartis Investigative Site
Berlin, 13353, Germany
Novartis Investigative Site
Berlin, 13405, Germany
Novartis Investigative Site
Bonn, 53115, Germany
Novartis Investigative Site
Cologne, 50937, Germany
Novartis Investigative Site
Cologne, 51065, Germany
Novartis Investigative Site
Dresden, 01277, Germany
Novartis Investigative Site
Dresden, 01307, Germany
Novartis Investigative Site
Erfurt, 99089, Germany
Novartis Investigative Site
Frankfurt, 60389, Germany
Novartis Investigative Site
Freiburg im Breisgau, 79106, Germany
Novartis Investigative Site
Göttingen, 37075, Germany
Novartis Investigative Site
Hamburg, 22291, Germany
Novartis Investigative Site
Heidelberg, 69115, Germany
Novartis Investigative Site
Kiel, 24105, Germany
Novartis Investigative Site
Koblenz, 56068, Germany
Novartis Investigative Site
Koeln-Nippes, 50733, Germany
Novartis Investigative Site
Leverkusen, 51375, Germany
Novartis Investigative Site
Ludwigsburg, 71634, Germany
Novartis Investigative Site
Ludwigshafen, 67063, Germany
Novartis Investigative Site
München, 81675, Germany
Novartis Investigative Site
Neuwied, 56564, Germany
Novartis Investigative Site
Nienburg, 31582, Germany
Novartis Investigative Site
Rotenburg an der Fulda, 36199, Germany
Novartis Investigative Site
Rüdersdorf, 15562, Germany
Novartis Investigative Site
Siegen, 57072, Germany
Novartis Investigative Site
Ulm, 89077, Germany
Novartis Investigative Site
Villingen-Schwenningen, 78052, Germany
Novartis Investigative Site
Worms, 67550, Germany
Novartis Investigative Site
Wuppertal, 42117, Germany
Novartis Investigative Site
Würzburg, 97080, Germany
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 9, 2016
First Posted
May 11, 2016
Study Start
July 12, 2016
Primary Completion
November 25, 2019
Study Completion
November 25, 2019
Last Updated
October 8, 2021
Results First Posted
October 9, 2020
Record last verified: 2021-10
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.