GISSI-HF- Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF

This study has been completed.
Sponsor:
Information provided by:
Gruppo di Ricerca GISSI
ClinicalTrials.gov Identifier:
NCT00336336
First received: June 12, 2006
Last updated: September 14, 2010
Last verified: September 2010
  Purpose

INTRODUCTION While pharmacological treatments specifically targeted to the cardio-circulatory system have been largely investigated, scanty controlled data are available concerning the role of dietary and metabolic approaches in the management/outcome of patients with heart failure. A large scale, randomized, clinical trial is proposed to test the effects of (a) n-3 PUFA and (b) a lipid lowering agent on top of the best recommended treatments for heart failure.

STUDY DESIGN

The GISSI-HF is a prospective, multicenter, randomized, double blind, placebo controlled study, with randomized allocation of patients with a clinical diagnosis of heart failure to:

Randomization 1 (R1): n-3 PUFA 1 g daily vs corresponding placebo; Randomization 2 (R2): rosuvastatin 10 mg daily vs corresponding placebo.

OBJECTIVES OF THE STUDY PRIMARY OBJECTIVES

To demonstrate that, in patients with heart failure treated at the best of recommended therapies, long term administration of (a) n-3 PUFA, (b) rosuvastatin is more effective than the corresponding placebo in the reduction of:

  • All-cause mortality
  • All-cause mortality or hospitalizations for cardiovascular reason

OTHER END-POINT MEASURES OF EFFICACY

To assess that long term administration of (a) n-3 PUFA, (b) rosuvastatin is more effective than corresponding placebo in the reduction of:

  • Cardiovascular mortality
  • Cardiovascular mortality or hospitalizations for any reason
  • Sudden cardiac death
  • Hospitalizations for any reason
  • Hospitalizations for cardiovascular reasons
  • Hospitalizations for congestive heart failure
  • Myocardial infarction
  • Stroke

Condition Intervention Phase
Heart Failure
Drug: n-3 PUFA
Drug: Rosuvastatin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Large Scale Clinical Trial Testing the Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic Congestive Heart Failure

Resource links provided by NLM:


Further study details as provided by Gruppo di Ricerca GISSI:

Primary Outcome Measures:
  • All-cause mortality [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]
  • All cause mortality or hospitalizations for any reason [ Time Frame: from enrollment to 1252 deaths ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cardiovascular mortality [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]
  • Cardiovascular mortality or hospitalization for heart failure or for any reasons [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]
  • Sudden cardiac death [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]
  • Hospitalizations for any reasons [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]
  • Hospitalization for Cardiovascular reasons [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]
  • Hospitalization for congestive heart failure [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]
  • Miocardial infarction [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]
  • Stroke [ Time Frame: from enrollment to 1252 deaths in R2 arm ] [ Designated as safety issue: No ]

Enrollment: 6975
Study Start Date: August 2002
Study Completion Date: May 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
N-3PUFA
Drug: n-3 PUFA
1 g die per os
Placebo Comparator: 2 Drug: Placebo
1 gram c. per os
Experimental: 3
Rosuvastatin
Drug: Rosuvastatin
10 mg die per os
Placebo Comparator: 4 Drug: Placebo
10 mg c. per os

Detailed Description:

The Protocol is sponsored by an independent organization and partially supported by: AstraZeneca, Società Prodotti antibiotici, Sigma Tau, Pfizer

  Eligibility

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

Inclusion Criteria:

  • Clinical evidence of heart failure according to the European Society of Cardiology guidelines (New York Heart Association class II-IV) (32)
  • Any left ventricular Ejection Fraction (EF) measured within 3 months from enrolment (if EF% >40%, at least 1 hospital admission for Congestive Heart Failure(CHF) in the previous year)
  • No age limits
  • Any etiology
  • Informed consent (obtained before any study specific procedure)

Exclusion Criteria:

COMMON EXCLUSION CRITERIA (R1=n-3 PUFA vs placebo and R2=rosuvastatin vs placebo):

  • Acute Myocardial Infarction, unstable angina or revascularization procedure within 1 month;
  • planned cardiac surgery, expected to be performed within 3 months;
  • congenital or primary valvular etiology;
  • known hypersensitivity to study treatments;
  • significant liver disease;
  • pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception;
  • any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol;
  • presence of any non-cardiac disease (e.g. cancer) that is likely to significantly shorten life expectancy;
  • treatment with any investigational agent within 1 month before randomization;
  • patients already on treatment with n-3 PUFA or statin for whom the prescription is confirmed.

EXCLUSION CRITERIA FOR R2 (statin hypothesis):

  • current serum creatinine level >2.5 mg/dL;
  • current ALT, AST level >1.5 times the upper normal limit;
  • current CPK upper normal limits.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00336336

  Show 338 Study Locations
Sponsors and Collaborators
Gruppo di Ricerca GISSI
Investigators
Study Chair: Luigi Tavazzi, MD Policlinico San Matteo di Pavia
Study Chair: Gianni Tognoni, MD Consorzio Mario Negri Sud
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Aldo P. Maggioni, Heart Care Foundation Onlus
ClinicalTrials.gov Identifier: NCT00336336     History of Changes
Other Study ID Numbers: G105
Study First Received: June 12, 2006
Last Updated: September 14, 2010
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014