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

Primary Purpose

Dilated Cardiomyopathy, Heart Failure

Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
n-3 PUFAs
Placebo
Sponsored by
Università degli Studi di Brescia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dilated Cardiomyopathy focused on measuring n-3 PUFAs, Heart Failure, Dilated cardiomyopathy, Ejection Fraction, Exercise Capacity

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arrhytmias and Heart failure Unit-Spedali Civili Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

n-3 PUFAs

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
October 18, 2010
Last Updated
January 27, 2012
Sponsor
Università degli Studi di Brescia
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1. Study Identification

Unique Protocol Identification Number
NCT01223703
Brief Title
PUFAs and Left Ventricular Function in Heart Failure
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Università degli Studi di Brescia

4. Oversight

Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dilated Cardiomyopathy, Heart Failure
Keywords
n-3 PUFAs, Heart Failure, Dilated cardiomyopathy, Ejection Fraction, Exercise Capacity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
133 (Actual)

8. Arms, Groups, and Interventions

Arm Title
n-3 PUFAs
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
n-3 PUFAs
Other Intervention Name(s)
OMACOR, Pronova Biopharma, Lysaker, Norway
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in Left Ventricular (LV) Systolic Function Expressed as Left Ventricular Ejection Fraction (LVEF) Between Baseline and 12-month Follow-up
Description
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
Time Frame
one year
Secondary Outcome Measure Information:
Title
LV Diastolic Function
Description
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.
Time Frame
one year
Title
Functional Capacity (Change in Peak Oxygen Uptake, VO2)
Description
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.
Time Frame
one year
Title
Change in Mean New York Heart Association (NYHA) Functional Class Between Baseline and 12th Month Follow up.
Description
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.
Time Frame
one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Savina Nodari, MD
Organizational Affiliation
Department of Experimental and Applied Medicine-Section of Cardiovascular Diseases
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Livio Dei Cas, MD
Organizational Affiliation
Department of Experimental and Applied Medicine-Section of Cardiovascular Diseases
Official's Role
Study Director
Facility Information:
Facility Name
Arrhytmias and Heart failure Unit-Spedali Civili Hospital
City
Brescia
ZIP/Postal Code
25100
Country
Italy

12. IPD Sharing Statement

Citations:
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.
Results Reference
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PUFAs and Left Ventricular Function in Heart Failure

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