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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01035255
First received: December 16, 2009
Last updated: September 9, 2015
Last verified: September 2015

December 16, 2009
September 9, 2015
December 2009
May 2014   (final data collection date for primary outcome measure)
Number of Participants That Had First Occurrence of the Composite Endpoint, Which is Defined as Either Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization [ Time Frame: up to 51 months ] [ Designated as safety issue: No ]
Number of participants that had first occurrence of the composite endpoint, which is defined as either CV death or HF hospitalization due to HF.
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 ]
Complete list of historical versions of study NCT01035255 on ClinicalTrials.gov Archive Site
  • Number of Patients - All-cause Mortality [ Time Frame: up to 51 months ] [ Designated as safety issue: Yes ]
    Number of patients - All-cause mortality. All-cause mortality is common in Heart Failure HF patients this measures how many patients had this event. The data is on FAS population up to March 31, 2014
  • Number of Patients Reported With Adjudicated Primary Causes of Death [ Time Frame: up to 51 months ] [ Designated as safety issue: Yes ]
    Number of patients reported with adjudicated primary causes of death. The data is on Randomization population up to March 31, 2014
  • Change From Baseline to Month 8 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score [ Time Frame: Baseline, Month 8 ] [ Designated as safety issue: No ]
    Change from baseline to Month 8 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score. KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. KCCQ clinical summary score is a composite assessment of physical limitations and total symptom scores. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
  • Number of Patients With First Confirmed Renal Dysfunction [ Time Frame: up to 51 months ] [ Designated as safety issue: No ]
    Number of patients with first confirmed renal dysfunction
  • Percentage of Participants With New Onset of Atrial Fibrillation (AF) [ Time Frame: up to 51 months ] [ Designated as safety issue: No ]
    Percentage of participants with New Onset of Atrial Fibrillation The new onset atrial fibrillation (AF) analysis was based on a subset of FAS: i.e., for patients without a history of AF at baseline (patients with a history of AF were excluded from this analysis).
  • 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 ]
Not Provided
Not Provided
 
This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure
A 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
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 =< 35%).
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Heart Failure With Reduced Ejection Fraction
  • Drug: LCZ696 200 mg BID
    LCZ696 200 mg BID
  • Drug: Enalapril 10 mg BID
    Enalapril 10 mg BID
  • Experimental: LCZ696
    single-blind active run-in period consisted of treatment with enalapril 10 mg bid, followed by LCZ696 100 mg bid, and then LCZ696 200 mg bid over a total duration of 5 to 10 weeks. Temporary down-titration from LCZ696 200 mg bid to LCZ696 100 mg bid was allowed provided the patient was up-titrated back to LCZ696 200 mg bid and tolerated this dose for at least two weeks before being eligible for randomization. LCZ696 200mg BID during double blind treatment period
    Intervention: Drug: LCZ696 200 mg BID
  • Active Comparator: Enalapril
    single-blind active run-in period consisted of treatment with enalapril 10 mg bid, followed by LCZ696 100 mg bid, and then LCZ696 200 mg bid over a total duration of 5 to 10 weeks. Temporary down-titration from LCZ696 200 mg bid to LCZ696 100 mg bid was allowed provided the patient was up-titrated back to LCZ696 200 mg bid and tolerated this dose for at least two weeks before being eligible for randomization. Enalapril 10 mg BID during double blind treatment period
    Intervention: Drug: Enalapril 10 mg BID

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
8442
May 2014
May 2014   (final data collection date for primary outcome measure)

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 =< 35%) 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.

Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Czech Republic,   Denmark,   Dominican Republic,   Ecuador,   Estonia,   Finland,   France,   Germany,   Guatemala,   Hong Kong,   Hungary,   Iceland,   India,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   Netherlands,   Panama,   Peru,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   United Kingdom,   Venezuela
Australia,   New Zealand,   Serbia,   Ukraine
 
NCT01035255
CLCZ696B2314, 2009-015834-31
Not Provided
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP