PUFAs and Left Ventricular Function in Heart Failure

Heart Failure Clinical Trial

— CS-PUFA-02  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01223703
• Other study ID #: CS-PUFA-02
• Status: Completed
• Phase: Phase 3
• First received: October 18, 2010
• Last updated: January 27, 2012
• Start date: November 2007
• Est. completion date: June 2009

Study information

• Verified date: January 2012
• Source: Università degli Studi di Brescia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy
• Heart Failure

Intervention

Drug:
• 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.
• 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

Locations

Country	Name	City	State
Italy	Arrhytmias and Heart failure Unit-Spedali Civili Hospital	Brescia

Sponsors (1)

Lead Sponsor	Collaborator
Università degli Studi di Brescia

Country where clinical trial is conducted

Italy, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Left Ventricular (LV) Systolic Function Expressed as Left Ventricular Ejection Fraction (LVEF) Between Baseline and 12-month Follow-up	The primary end point of the study was the change in LV systolic function expressed as LVEF between baseline and 12-month follow-up. The following parameters were measured according to the professional standards defined by the American Society of Echocardiography and the European Association of Echocardiography	one year	No
Secondary	LV Diastolic Function	Change in LV diastolic function assessed by echocardiography: mitral diastolic inflow velocities (peak velocity of early ventricular filling [E-wave], peak velocity of late ventricular filling [A-wave], E/A ratio, and E-wave deceleration time), diastolic function score (graded on a scale from 1 to 4) were used.	one year	No
Secondary	Functional Capacity (Change in Peak Oxygen Uptake, VO2)	Change in functional capacity expressed as a peak oxygen uptake (VO2), that was acquired breath-by-breath by pneumotachograph (with bidirectional differential pressure) during cardiopulmonary exercize testing.	one year	No
Secondary	Change in Mean New York Heart Association (NYHA) Functional Class Between Baseline and 12th Month Follow up.	NYHA class I: No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs, etc...; NYHA class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.; NYHA class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest NYHA class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.	one year	No