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

Study Overview
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Brief Summary
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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

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

Official Title
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A Large Scale Clinical Trial Testing the Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic Congestive Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: n-3 PUFA
* Drug: Rosuvastatin
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>N-3PUFA | Drug: n-3 PUFA<br>* 1 g die per os<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* 1 gram c. per os<br>|
| Experimental: 3<br>Rosuvastatin | Drug: Rosuvastatin<br>* 10 mg die per os<br>|
| Placebo Comparator: 4<br> | Drug: Placebo<br>* 10 mg c. per os<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | from enrollment to 1252 deaths in R2 arm | 
| All cause mortality or hospitalizations for any reason |  | from enrollment to 1252 deaths | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular mortality |  | from enrollment to 1252 deaths in R2 arm | 
| Cardiovascular mortality or hospitalization for heart failure or for any reasons |  | from enrollment to 1252 deaths in R2 arm | 
| Sudden cardiac death |  | from enrollment to 1252 deaths in R2 arm | 
| Hospitalizations for any reasons |  | from enrollment to 1252 deaths in R2 arm | 
| Hospitalization for Cardiovascular reasons |  | from enrollment to 1252 deaths in R2 arm | 
| Hospitalization for congestive heart failure |  | from enrollment to 1252 deaths in R2 arm | 
| Miocardial infarction |  | from enrollment to 1252 deaths in R2 arm | 
| Stroke |  | from enrollment to 1252 deaths in R2 arm |