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
Results First Received: August 6, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Heart Failure With Reduced Ejection Fraction
Interventions: Drug: LCZ696 200 mg BID
Drug: Enalapril 10 mg BID

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
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
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

Participant Flow:   Overall Study
    LCZ696     Enalapril  
STARTED     4209     4233  
GCP Violations     18     19  
Mis-randomized     4     2  
Full Analysis Set (FAS)     4187 [1]   4212 [1]
COMPLETED     3468     3371  
NOT COMPLETED     741     862  
Death                 724                 844  
Lost to Follow-up                 2                 5  
patient's request                 15                 13  
[1] patents with GCP violation and mis-randomized are not included in FAS



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
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
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
Total Total of all reporting groups

Baseline Measures
    LCZ696     Enalapril     Total  
Number of Participants  
[units: participants]
  4209     4233     8442  
Age  
[units: years]
Mean (Standard Deviation)
  63.78  (11.520)     63.82  (11.25)     63.80  (11.385)  
Gender  
[units: participants]
     
Female     888     959     1847  
Male     3321     3274     6595  



  Outcome Measures
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1.  Primary:   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 ]

2.  Secondary:   Number of Patients - All-cause Mortality   [ Time Frame: up to 51 months ]

3.  Secondary:   Number of Patients Reported With Adjudicated Primary Causes of Death   [ Time Frame: up to 51 months ]

4.  Secondary:   Change From Baseline to Month 8 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score   [ Time Frame: Baseline, Month 8 ]

5.  Secondary:   Number of Patients With First Confirmed Renal Dysfunction   [ Time Frame: up to 51 months ]

6.  Secondary:   Percentage of Participants With New Onset of Atrial Fibrillation (AF)   [ Time Frame: up to 51 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:
Packer M, McMurray JJ, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile M, Andersen K, Arango JL, Arnold JM, Bělohlávek J, Böhm M, Boytsov S, Burgess LJ, Cabrera W, Calvo C, Chen CH, Dukat A, Duarte YC, Erglis A, Fu M, Gomez E, Gonzàlez-Medina A, Hagège AA, Huang J, Katova T, Kiatchoosakun S, Kim KS, Kozan Ö, Llamas EB, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires FJ, Refsgaard J, Rosenthal A, Senni M, Sibulo AS Jr, Silva-Cardoso J, Squire IB, Starling RC, Teerlink JR, Vanhaecke J, Vinereanu D, Wong RC; PARADIGM-HF Investigators and Coordinators. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015 Jan 6;131(1):54-61. doi: 10.1161/CIRCULATIONAHA.114.013748. Epub 2014 Nov 17.


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01035255     History of Changes
Other Study ID Numbers: CLCZ696B2314
2009-015834-31
Study First Received: December 16, 2009
Results First Received: August 6, 2015
Last Updated: September 9, 2015
Health Authority: United States: Food and Drug Administration
Argentina: National Administration of Drugs, Foods and Medical Technology
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: Ministry of Health
Bulgaria: Ministry of Health
Canada: Health Canada
Chile: Comisión Nacional de Investigación Científica y Tecnológica
China: Food and Drug Administration
Colombia: National Institute of Food and Drug Vigilance
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Ecuador: Public Health Ministry
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Sanitary Safety of Health Products Agency
Germany: Federal Institute for Drugs and Medical Devices
Guatemala: Ministry of health
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Iceland: Icelandic Medicines Control Agency
India: Central Drug Standard Organization
Israel: Ministry of Health
Italy: National Institute of Health
Korea: Korea Food and Drug Administration
Latvia: State Agency of Medicines
Lithuania: State Medicines Control Agency
Malaysia: Ministry of Health
Mexico: Ministry of Health
Netherlands: Medicines Evaluation Board
Panama: Ministry of Health
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Philippines: Bureau of Food and Drugs
Poland: Ministry of Health
Portugal: National Institute of Pharmacy and Medicines
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Singapore: Center for Drug Administration
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Drug Agency
Sweden: Medical Products Agency
Taiwan: Department of Health
Thailand: Ministry of Public Health
Turkey: General Directorate of Pharmaceuticals and Pharmacy
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Venezuela: Ministry of Health and Social Development
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Belgium: Federal Agency for Medicinal Products and Health Products
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Guatemala: Ministry of Public Health and Social Assistance
India: Central Drugs Standard Control Organization
Korea: Food and Drug Administration
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Portugal: National Pharmacy and Medicines Institute
Spain: Spanish Agency of Medicines