NCT03066804

A Randomized, Double-blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Patients

A 24-week, Randomized, Double-blind, Multi-center, Parallel LCZ696 on NT-proBNP, Exercise Capacity, Symptoms and Safety Compared to Individualized Medical Management of Comorbidities in Patients With Heart Failure and Preserved Ejection Fraction

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2,572 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 45 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to demonstrate the superiority of LCZ696 over individualized medical therapy for comorbidities in reducing N-terminal pro-brain natriuretic peptide (NT-proBNP) and improving exercise capacity and HF symptoms in patients with heart failure with preserved ejection fraction (HFpEF).

Detailed description

This study was a 24-week, randomized, double-blind, multi-center, parallel group, active controlled study to evaluate sacubitril/valsartan compared to individualized medical therapy on NT proBNP, exercise capacity, symptoms and QoL in patients with heart failure and preserved left ventricular ejection (HFpEF) fraction (LVEF \> 40%). Patients were initially stratified into one of three strata according to prior treatment for comorbidities: Angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or no prior renin angiotensin system inhibitors (RASi). Patients in each stratum were randomized in a 1:1 ratio and received either sacubitril/valsartan or comparator (i.e. enalapril for patients in ACEi strata, valsartan for patients in the ARB strata and placebo for patients in the No RASi strata). There was no designated proportion of patients planned in each stratum; the strata were populated based upon the patient's prior treatment regimen. The study consisted of a screening epoch of up to 2 weeks and a randomized treatment epoch of 24 weeks, which included a 1 to 4 week study drug up-titration epoch followed by a 20 to 23 week maintenance epoch. Uptitration to target doses was recommended to occur within the first four weeks of the study, and was performed by Investigator's discretion based on the patient's clinical status.

Conditions

• Heart Failure With Preserved Ejection Fraction

Interventions

Type	Name	Description
DRUG	sacubitril/valsartan	Sacubitril/valsartan is available as 24 mg/26 mg, 49 mg/51 mg, 97 mg/103 mg, respectively in tablet form to be taken orally
DRUG	Enalapril	Enalapril is available as 2.5 mg, 5 mg, and 10 mg tablet form to be taken orally
DRUG	Valsartan	Valsartan is available as 40 mg, 80 mg, 160 mg tablet form to be taken orally
DRUG	Placebo to match sacubitril/valsartan	Placebo to match LCZ696 50 mg, 100 mg, 200 mg tablet form to be taken orally
DRUG	Placebo to match enalapril	Placebo to match enalapril 2.5 mg, 5 mg, 10 mg tablet form to be taken orally
DRUG	Placebo to match valsartan	Placebo to match valsartan 40 mg, 80 mg, 160 mg tablet form to be taken orally

Timeline

• Start date: 2017-08-22
• Primary completion: 2019-10-28
• Completion: 2019-10-28
• First posted: 2017-02-28
• Last updated: 2021-10-11
• Results posted: 2021-02-08

Locations

380 sites across 32 countries: United States, Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Colombia, Czechia, Denmark, Estonia, France, Germany, Guatemala, Hungary, India, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, Peru, Portugal, Romania, Russia, Serbia, Slovakia, Spain, Thailand, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study