PUFAs and Left Ventricular Function in Heart Failure (CS-PUFA-02)

• ClinicalTrials.gov Identifier: NCT01223703
• Recruitment Status: Completed
• First Posted: October 19, 2010
• Results First Posted: July 25, 2011
• Last Update Posted: January 31, 2012
• Sponsor: Università degli Studi di Brescia
• Information provided by (Responsible Party): Savina Nodari, Università degli Studi di Brescia

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Dilated Cardiomyopathy; Heart Failure	Drug: n-3 PUFAs; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 133 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of n-3 Polyunsaturated Fatty Acids (PUFAs) on Left Ventricular Function and Functional Capacity in Patients With Dilated Cardiomyopathy
• Study Start Date: November 2007
• Actual Primary Completion Date: June 2009
• Actual Study Completion Date: June 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: n-3 PUFAs	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.; Other Name: OMACOR, Pronova Biopharma, Lysaker, Norway
Placebo Comparator: Placebo	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

Outcome Measures

Primary Outcome Measures :

1. Change in Left Ventricular (LV) Systolic Function Expressed as Left Ventricular Ejection Fraction (LVEF) Between Baseline and 12-month Follow-up [ Time Frame: one year ]
   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

Secondary Outcome Measures :

1. LV Diastolic Function [ Time Frame: one year ]
   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.
2. Functional Capacity (Change in Peak Oxygen Uptake, VO2) [ Time Frame: one year ]
   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.
3. Change in Mean New York Heart Association (NYHA) Functional Class Between Baseline and 12th Month Follow up. [ Time Frame: one year ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Italy

Arrhytmias and Heart failure Unit-Spedali Civili Hospital

Brescia, Italy, 25100

Sponsors and Collaborators

Università degli Studi di Brescia

Investigators

• Principal Investigator: Savina Nodari, MD; Department of Experimental and Applied Medicine-Section of Cardiovascular Diseases
• Study Director: Livio Dei Cas, MD; Department of Experimental and Applied Medicine-Section of Cardiovascular Diseases

More Information

Publications:

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.

• Responsible Party: Savina Nodari, Effects of n-3 Polyunsaturated Fatty Acids (PUFAs) on Left Ventricular Function and Functional Capacity in Patients With Dilated Cardiomyopathy, Università degli Studi di Brescia
• ClinicalTrials.gov Identifier: NCT01223703
• Other Study ID Numbers: CS-PUFA-02
• First Posted: October 19, 2010
• Results First Posted: July 25, 2011
• Last Update Posted: January 31, 2012
• Last Verified: January 2012

Keywords provided by Savina Nodari, Università degli Studi di Brescia:

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

Additional relevant MeSH terms:

Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated; Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Laminopathies; Genetic Diseases, Inborn