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

Condition(s) targeted: Heart Failure

Intervention: n-3 PUFA (Drug); Rosuvastatin (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Gruppo di Ricerca GISSI

Official(s) and/or principal investigator(s):
Luigi Tavazzi, MD, Study Chair, Affiliation: Policlinico San Matteo di Pavia
Gianni Tognoni, MD, Study Chair, Affiliation: Consorzio Mario Negri Sud

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

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

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety Study

Primary outcome:

All-cause mortality at the end of follow-up period.

All cause mortality or hospitalizations for any reason at the end of follow-up period

Since the trial is event driven, the follow-up period will be completed when 1252 deaths

(number needed to allow a reliable evaluation of the efficacy of tested drugs for both R1 and R2) will occur.

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Clinical evidence of heart failure according to the ESC guidelines (NYHA class II-IV)

(32)

- Any left ventricular EF measured within 3 months from enrolment (if EF% >40%, at least

1 hospital admission for 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):

- AMI, 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.

Related publications:

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.

Starting date: August 2002
Last updated: January 12, 2007