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PARADIGM-HF

A large trial in adults with heart failure and a reduced ejection fraction (40% or less). It compared LCZ696, a combination of sacubitril and valsartan, with enalapril, an ACE inhibitor, each added to recommended treatment. The trial was stopped early, because the prespecified boundary for overwhelming benefit with LCZ696 was crossed. Fewer people on LCZ696 died from cardiovascular causes or were admitted to hospital for heart failure. Low blood pressure and nonserious angioedema were more common with LCZ696.

Also called LCZ696 versus enalapril in heart failure trial

  • Study
  • In this atlas

Overview

Design
Randomized, parallel-group, double-blind, active-controlled phase 3 trial comparing LCZ696 200 mg twice daily with enalapril 10 mg twice daily, each added to recommended therapy. The registry records masking as double and describes a single-blind run-in period before randomization.
Phase
Phase 3
Enrolled
  • 8,442 patients (randomized count) (Angiotensin-neprilysin inhibition versus enalapril in heart failure, retrieved )
Sponsor
  • Novartis Lead sponsor on the registry record
Funder
Not recorded
Registry
  • NCT NCT01035255
Started
(This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, retrieved )
Primary completion
(actual) (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, retrieved )
Completion
(actual) (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, retrieved )
Results first posted
(This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, retrieved )
Countries
United States, Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Denmark, Dominican Republic, Ecuador, Estonia, Finland, France, Germany, Guatemala, Hungary, Iceland, India, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Panama, Peru, Philippines, Poland, Portugal, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, United Kingdom, Venezuela, Hong Kong SAR China, Türkiye (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, retrieved )
Care setting
Not reported
Registry status
  • “TERMINATED” (U.S. National Library of Medicine (ClinicalTrials.gov), retrieved )
Stopped early
The trial stopped early, date not reported. The abstract says the trial was stopped early, under prespecified rules and after a median follow-up of 27 months, because the boundary for overwhelming benefit with LCZ696 had been crossed. The registry records the status as terminated and gives the same reason, after a final prespecified interim analysis on 28 March 2014. (Angiotensin-neprilysin inhibition versus enalapril in heart failure, retrieved )

Technical summary

Novartis-sponsored, randomized, double-blind, active-controlled phase 3 trial (NCT01035255) of 8442 patients with NYHA class II to IV heart failure and an ejection fraction of 40% or less. Stopped early after a median follow-up of 27 months. Primary outcome: cardiovascular death or hospitalization for heart failure in 914 patients (21.8%) with LCZ696 and 1117 (26.5%) with enalapril, hazard ratio 0.80 (95% CI 0.73 to 0.87), from the PubMed abstract. The PubMed record indexes LCZ696 as the sacubitril and valsartan drug combination. The registry status is terminated and the registry gives no start-date type. The full text was not read. Funding is stated in the abstract as Novartis. The registry lists Novartis Pharmaceuticals as lead sponsor, and this record links to the Novartis organization record.

Arms

  • LCZ696 (sacubitril/valsartan)

    Intervention Sacubitril/valsartan (combination)

    LCZ696 200 mg twice daily, added to recommended therapy (abstract). The registry says randomization followed a single-blind run-in on enalapril and then LCZ696.

  • Enalapril

    Intervention None named

    Enalapril 10 mg twice daily, added to recommended therapy (abstract). The same run-in came before randomization (registry).

Findings

No findings are published for this study.

Record details

Record id
cardio:paradigm-hf
Content hash
8f35e30813b77578c7076affad517bfd7ac4ce30ff4c1d8dbef566ee0b2c0226