Clinical trial NCT01223703: PUFAs and Left Ventricular Function in Heart Failure
Official title: Effects of n-3 Polyunsaturated Fatty Acids (PUFAs) on Left Ventricular Function and Functional Capacity in Patients With Dilated Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dilated Cardiomyopathy
Heart Failure
Keywords: n-3 PUFAs
Heart Failure
Dilated cardiomyopathy
Ejection Fraction
Exercise Capacity
Lead sponsor: Università degli Studi di Brescia
Sponsor class: OTHER
First posted: 2010-10-19
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Left Ventricular (LV) Systolic Function Expressed as Left Ventricular Ejection Fraction (LVEF) Between Baseline and 12-month Follow-up
timeFrame: one year
Secondary outcomes:
measure: LV Diastolic Function
timeFrame: one year
measure: Functional Capacity (Change in Peak Oxygen Uptake, VO2)
timeFrame: one year
measure: Change in Mean New York Heart Association (NYHA) Functional Class Between Baseline and 12th Month Follow up.
timeFrame: one year
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: Arrhytmias and Heart failure Unit-Spedali Civili Hospital
Study officials:
affiliation: Department of Experimental and Applied Medicine-Section of Cardiovascular Diseases
name: Savina Nodari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Experimental and Applied Medicine-Section of Cardiovascular Diseases
name: Livio Dei Cas, MD
role: STUDY_DIRECTOR
References:
citation: 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.