Clinical trial NCT02768298: Exercise Capacity Study of LCZ696 vs. Enalapril in Patients With Chronic Heart Failure and Reduced Ejection Fraction.
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Heart Failure With Reduced Ejection Fraction
Keywords: LCZ696
sacubitril/valsartan
VO2peak
heart failure
systolic heart failure
heart failure with reduced ejection fraction
exercise capacity
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-05-11
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Peak Respiratory Oxygen Uptake (VO2peak) Adjusted to Body Weight) After 3 Months of Treatment
timeFrame: Baseline, 3 months
Secondary outcomes:
measure: Change From Baseline in Peak Respiratory Oxygen Uptake (VO2peak) Adjusted to Body Weight) After 6 Weeks of Treatment
timeFrame: Baseline, 6 weeks
measure: Change From Baseline in the Minute Ventilation (VE) to Carbon Dioxide Output Slope (VE/VCO2 Slope)
timeFrame: Baseline, 6 weeks, 3 months
measure: Change From Baseline in Exercise Capacity (Watt) at Ventilatory Anaerobic Threshold (VAT)
timeFrame: Baseline, 6 weeks, 3 months
measure: Change From Baseline in Rate of Perceived Exertion (Perceived Dyspnea and Perceived Fatigue) During Exercise Assessed by Borg Scale
timeFrame: Baseline, 3 months
Other outcomes:
Locations:
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Dresden
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erfurt
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Koblenz
country: Germany
facility: Novartis Investigative Site
city: Koeln-Nippes
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Leverkusen
country: Germany
facility: Novartis Investigative Site
city: Ludwigsburg
country: Germany
facility: Novartis Investigative Site
city: Ludwigshafen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Neuwied
country: Germany
facility: Novartis Investigative Site
city: Nienburg
country: Germany
facility: Novartis Investigative Site
city: Rotenburg an der Fulda
country: Germany
facility: Novartis Investigative Site
city: Rüdersdorf
country: Germany
facility: Novartis Investigative Site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Villingen-Schwenningen
country: Germany
facility: Novartis Investigative Site
city: Worms
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Wuppertal
country: Germany
facility: Novartis Investigative Site
Study officials:
References: