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

Sponsor:	Gruppo di Ricerca GISSI
Information provided by:	Gruppo di Ricerca GISSI
ClinicalTrials.gov Identifier:	NCT00336336

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety Study
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:

MedlinePlus related topics: Heart Failure

Drug Information available for: Rosuvastatin calcium Rosuvastatin

U.S. FDA Resources

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
1: Experimental N-3PUFA	Drug: n-3 PUFA 1 g die per os
2: Placebo Comparator	Drug: Placebo 1 gram c. per os
3: Experimental Rosuvastatin	Drug: Rosuvastatin 10 mg die per os
4: Placebo Comparator	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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00336336

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:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Gissi-Hf Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Aug 29; [Epub ahead of print]

Gissi-Hf Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Aug 29; [Epub ahead of print]

Tavazzi L, Tognoni G, Franzosi MG, Latini R, Maggioni AP, Marchioli R, Nicolosi GL, Porcu M; GISSI-HF Investigators. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail. 2004 Aug;6(5):635-41.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Maggioni AP, Fabbri G, Lucci D, Marchioli R, Franzosi MG, Latini R, Nicolosi GL, Porcu M, Cosmi F, Stefanelli S, Tognoni G, Tavazzi L; GISSI-HF Investigators. Effects of rosuvastatin on atrial fibrillation occurrence: ancillary results of the GISSI-HF trial. Eur Heart J. 2009 Oct;30(19):2327-36. Epub 2009 Aug 30.

Responsible Party:	Heart Care Foundation Onlus ( Aldo P. Maggioni )
Study ID Numbers:	G105
Study First Received:	June 12, 2006
Last Updated:	September 2, 2008
ClinicalTrials.gov Identifier:	NCT00336336 History of Changes
Health Authority:	Italy: Ministry of Health

Additional relevant MeSH terms:

Antimetabolites
Heart Failure
Rosuvastatin
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Antilipemic Agents
Enzyme Inhibitors
Cardiovascular Diseases
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2009