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 is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01035255
First received: December 16, 2009
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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%).


Condition Intervention Phase
Heart Failure With Reduced Ejection Fraction
Drug: LCZ696 200 mg BID
Drug: Enalapril 10 mg BID
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 8458
Study Start Date: December 2009
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696 200 mg BID
LCZ696 200mg BID
Drug: LCZ696 200 mg BID
LCZ696 200 mg BID
Active Comparator: Enalapril 10 mg BID
Enalapril 10 mg BID
Drug: Enalapril 10 mg BID
Enalapril 10 mg BID

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01035255

  Show 1042 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Last Updated: April 2, 2014
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

Keywords provided by Novartis:
chronic heart failure
cardiovascular death
hospitalization
outcome study
BNP
KCCQ
eGFR

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Enalapril
Enalaprilat
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014