This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure (PARADIGM-HF)


Tracking Information

Start Date  ICMJEDecember 2009
Estimated Primary Completion DateJuly 2013   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: December 17, 2009)		Time to first occurrence of the composite endpoint, which is defined as either CV death or HF hospitalization [ Time Frame: up to 4yrs ] [ Designated as safety issue: No ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT01035255 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: December 17, 2009)
  • Change in the clinical summary score for HF symptoms and physical limitations (as assessed by KCCQ). [ Time Frame: up to 4yrs ] [ Designated as safety issue: No ]
  • Time to all-cause mortality [ Time Frame: up to 4yrs ] [ Designated as safety issue: Yes ]
  • Time to occurrence of renal dysfunction [ Time Frame: up to 4yrs ] [ Designated as safety issue: No ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJEThis Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure
Official Title  ICMJEA Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic Heart Failure and Reduced Ejection Fraction
Brief Summary

The study will evaluate the efficacy and safety of LCZ696 compared to enalapril on morbidity and mortality in patients with chronic heart failure (NYHA Class II - IV and EF< 40%).

Detailed Description 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment
Condition  ICMJEHeart Failure With Reduced Ejection Fraction
Intervention  ICMJE
  • Drug: LCZ696 200 mg BID
    LCZ696 200 mg BID
  • Drug: Enalapril 10 mg BID
    Enalapril 10 mg BID
Study Arms / Comparison Groups
  • LCZ696 200 mg BID: Experimental
    LCZ696 200mg BID
    Intervention: Drug: LCZ696 200 mg BID
  • Enalapril 10 mg BID: Active Comparator
    Enalapril 10 mg BID
    Intervention: Drug: Enalapril 10 mg BID

Recruitment Information

Estimated Enrollment  ICMJE7980
Completion Date 
Estimated Primary Completion DateJuly 2013   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must give written informed consent before any assessment is performed.
  • Outpatients ≥ 18 years of age, male or female.
  • Patients with a diagnosis of CHF NYHA class II-IV and reduced ejection fraction (EF <40%) and elevated BNP.
  • Patients must 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.
  • Patients must be treated with a β-blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks.

Exclusion Criteria:

  • Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
  • 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 and/or a SBP < 100 mmHg.
  • Estimated GFR < 30 mL/min/1.73m2 as measured by the simplified MDRD formula
  • Serum potassium > 5.2 mmol/L.

Other protocol-defined inclusion/exclusion criteria may apply.

GenderBoth
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Novartis Pharmaceuticals862-778-8300
Location Countries  ICMJEUnited States,   Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Czech Republic,   Denmark,   Estonia,   Finland,   France,   Germany,   Guatemala,   Hungary,   Iceland,   India,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Panama,   Peru,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   Venezuela

Administrative Information

NCT ID  ICMJENCT01035255
Responsible PartyExternal Affairs, Novartis Pharmaceuticals
Study ID Numbers  ICMJECLCZ696B2314
Study Sponsor  ICMJENovartis
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:Novartis PharmaceuticalsNovartis Pharmaceuticals
Information Provided ByNovartis