Please select the eligibility criteria that correspond to the clinical trial below.
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
Brief Summary: 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


Options:
A: 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.
B: Inclusion Criteria:

* Both men and women
* Age \> 18 years
* Liver fat diagnosed on normal clinical grounds including in most cases liver assessed by Kleiner scoring system to classify severity, with no known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B \& C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis). Last liver biopsy will be within 3 years of recruitment to the study.
* Liver fat diagnosed by ultrasound, CT or magnetic resonance imaging (MRI) in patients who also have either diabetes and/or features of the metabolic syndrome, without evidence of known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B \& C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis).
* Alcohol consumption ≤ 14 units / week for women ≤ 21 units / week for men.

Exclusion Criteria:

* Alcohol consumption \> 15 units /week for women and \> 22 units /week for men.
* Decompensated acute or chronic liver disease.
* A history of viral hepatitis, diarrhoea, diverticulosis, irritable bowel syndrome, inflammatory bowel diseases, coeliac disease (seropositivity for anti-endomysial immunoglobulin A antibodies; immunoglobulin A (IgA) EMA).
* Previous bariatric or other abdominal surgery.
* Continuous use of antibiotics that may change gut microflora, probiotics, or antisecretory drugs capable of causing achlorhydria within the 2 months preceding enrolment, or evidence of immunoglobulin A or immunoglobulin deficiency (both of which produce confounding effects during assessments of intestinal permeability and small intestinal bacterial overgrowth).
C: Inclusion Criteria:

* Persistent atrial fibrillation

Exclusion Criteria:

* Contraindications or known hypersensitivity to n-3 PUFA
* Current treatment with n-3 PUFA for any reason
* Heart failure NYHA class IV
* Coronary artery bypass surgery or valve replacement within the past 3 months
* Planned cardiac procedures
* Known sick-sinus syndrome
* Diagnosis of Wolff-Parkinson-White
* Clinical significant valvular etiologies
* Presence of arrhythmia associated with an acute reversible condition
* Advanced chronic lung disease
* Contraindications for anticoagulation therapy
* Pregnancy or lactation
* Any non cardiac illness associated with a life expectancy of \< 2 years
* Treatment with any investigational agent within 3 month before randomization
* 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
D: Inclusion Criteria:

* Aged 21 years and older
* Have BMI \>30.0 kg/m2 and \<40 kg/m2
* Willing and able to participate in clinic visits, group sessions, and telephone and Internet communications at specified intervals
* Able to provide data through questionnaires and by telephone
* Willing to maintain contact with the investigators for 12 months
* Willing to allow blood collections
* No known allergy to tree nuts
* Able to be physically active

Exclusion Criteria:

* Diabetic
* Inability to be moderately physically active
* A history or presence of a comorbid diseases for which diet modification and increased physical activity may be contraindicated
* Currently pregnant/breastfeeding
* Planning to become pregnant within the next year
* Currently enrolled in a weight loss program or diet intervention study
* Current use of weight loss medication or supplements
* Planned surgical procedure that can impact the conduct of the study
* Have plans to relocate from area within the next year
* 6+ months use of meds likely to cause weight gain or prevent weight loss
* Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in this study

Answer: A