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

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

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.


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.


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


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
Drug: n-3 PUFA
1 g die per os
Placebo Comparator: 2 Drug: Placebo
1 gram c. per os
Experimental: 3
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


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

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.
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Please refer to this study by its identifier: NCT00336336

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

Additional Information:
Additional publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: Aldo P. Maggioni, Heart Care Foundation Onlus 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
Cardiovascular Diseases
Heart Diseases
Anticholesteremic Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses processed this record on July 28, 2015