PUFAs and Left Ventricular Function in Heart Failure

NCT ID: NCT01223703

Last Updated: 2012-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2009-06-30

Brief Summary

The purpose of this study is to test the hypothesis that n-3 PUFAs improve left ventricular systolic function in patients with stable chronic HF secondary to nonischemic dilated cardiomyopathy (NICM).

Detailed Description

The results of the GISSI-HF trial indicate that in patients with chronic HF on evidence-based medical therapy and New York Heart Association (NYHA) functional class II-IV, long term treatment with n-3 PUFAs 1 g daily reduces mortality and hospitalizations for cardiovascular reasons. Several potential mechanisms may underlie the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) in HF patients, including, but not limited to, antiarrhythmic, and hemodynamic actions. The current investigation was therefore designed to test the hypothesis that treatment with n-3 PUFAs improves LV systolic function expressed as EF in patients with stable chronic HF secondary to a nonischemic dilated cardiomyopathy (NICM). Additionally, we sought to determine if n-3 PUFAs also exert positive effects on LV diastolic function assessed by echocardiography; functional capacity assessed by cardiopulmonary stress testing (CPET); and New York Heart Association (NYHA) functional class.

Conditions

Dilated Cardiomyopathy; Heart Failure

Keywords

n-3 PUFAs; Heart Failure; Dilated cardiomyopathy; Ejection Fraction; Exercise Capacity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

n-3 PUFAs

Group Type: ACTIVE_COMPARATOR

n-3 PUFAs

Intervention Type: DRUG

1.0 g gelatin capsules containing 850 to 882 mg of EPA and DHA ethyl esters in the average ratio EPA/DHA of 0.9:1.5 The treatment dose was five capsules daily for the first month followed by two capsules daily for the rest of the study.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

1.0 g gelatin capsules containing olive oil. The treatment dose was five capsules daily for the first month followed by two capsules daily for the rest of the study

Interventions

n-3 PUFAs

1.0 g gelatin capsules containing 850 to 882 mg of EPA and DHA ethyl esters in the average ratio EPA/DHA of 0.9:1.5 The treatment dose was five capsules daily for the first month followed by two capsules daily for the rest of the study.

Intervention Type: DRUG

Placebo

1.0 g gelatin capsules containing olive oil. The treatment dose was five capsules daily for the first month followed by two capsules daily for the rest of the study

Intervention Type: DRUG

Other Intervention Names

OMACOR, Pronova Biopharma, Lysaker, Norway

Eligibility Criteria

Inclusion Criteria

• patients with a diagnosis of non ischemic cardiomyopathy (the absence of coronary artery disease,defined as the absence of stenosis > 50%, was confirmed by angiography performed at the time of the diagnostic workup of the cardiomyopathy)
• LV systolic dysfunction (defined as an EF < 45%)
• Stable clinical conditions with minimal or no symptoms for at least three month
• Evidence-based medical treatment at maximum tolerated target doses for at least six month

Exclusion Criteria

• presence of symptoms or evidence of CAD diagnosed through noninvasive tests;
• peripheral arterial disease;
• presence of congenital or primary valvular heart disease;
• persistent atrial fibrillation;
• inability to perform bicycle ergometry for noncardiac causes;
• moderately to severely reduced functional capacity;
• NYHA functional class IV;
• poor acoustic windows limiting the ability to assess echocardiographic measurements;
• chronic lung disease;
• advanced renal disease (eGFR < 30 mL/min/1.73 m2);
• advanced liver disease;
• any disease limiting life expectancy to one year or less;
• contraindications to study drugs;
• concomitant participation in other research studies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università degli Studi di Brescia

OTHER

Sponsor Role: lead

Responsible Party

Savina Nodari

Effects of n-3 Polyunsaturated Fatty Acids (PUFAs) on Left Ventricular Function and Functional Capacity in Patients With Dilated Cardiomyopathy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Savina Nodari, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Experimental and Applied Medicine-Section of Cardiovascular Diseases

Livio Dei Cas, MD

Role: STUDY_DIRECTOR

Department of Experimental and Applied Medicine-Section of Cardiovascular Diseases

Locations

Arrhytmias and Heart failure Unit-Spedali Civili Hospital

Brescia, , Italy

Countries

Italy

References

1.Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of n-3polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet2008;372:1223-30. 2.Duda MK, O'Shea KM, Tintinu A, et al. Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction. Cardiovasc Res 2009;81:319-27. 3.Duda MK, O'Shea KM, Lei B, et al. Dietary supplementation with omega-3 PUFA increases adiponectin and attenuates ventricular remodeling and dysfunction with pressure overload. Cardiovasc Res 2007;76:303-10. 4.Vargiu R, Littarru GP, Fraschini M, et al. Enhancement of shortening velocity, power, and acto-myosin crossbridge (CB) kinetics following long-term treatment with propionyl-L-carnitine, coenzyme Q10, and omega-3 fatty acids in BIO TO-2 cardiomyopathic Syrian hamsters papillary muscle. Biofactors 2010;36:229-39. 5.Pepe S, McLennan PL. Cardiac membrane fatty acid composition modulates myocardial oxygen consumption and postischemic recovery of contractile function. Circulation 2002;105:2303-8. 6.Duda MK, O'Shea KM, Stanley WC. omega-3 polyunsaturated fatty acid supplementation for the treatment of heart failure: mechanisms and clinical potential. Cardiovasc Res 2009;84:33-41.

Reference Type: BACKGROUND

Other Identifiers

CS-PUFA-02

Identifier Type: -

Identifier Source: org_study_id