Clinical trial NCT00597220: Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation
Official title: Randomized, Prospective, Placebo-controlled, Multi-center Study to Test the Efficacy of n-3 PUFA for the Maintenance of Normal Sinus Rhythm in Patients With Persistent Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Atrial Fibrillation
Lead sponsor: Fundacion GESICA
Sponsor class: OTHER
First posted: 2008-01-17
Enrollment: 1600
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To demonstrate that in patients with persistent atrial fibrillation who had recovered normal sinus rhythm and treated with the best recommended therapies, the addition of 1 gram / daily of n-3 PUFA is superior to the corresponding placebo for the maintenance of normal sinus rhythm at one year of follow up.

Detailed description: Atrial fibrillation (AF) impose a substantial and growing economic burden on health care expenditures. In patients with persistent AF, there are fundamentally two ways to manage the arrhythmia: to restore and maintain sinus rhythm (rhythm control) or to allow AF to continue and ensure that the ventricular rate is controlled (rate control). As it has been stated, it goes without saying that if we could prevent atrial fibrillation (AF) or restore and maintain sinus rhythm in patients suffering from persistent AF, without any penalties due to the unwanted effects of drugs or incomplete suppression of AF and its thromboembolic complications, every physician would do so. Current strategies however, are limited to achieve such desirable goal. In the last years a growing amount of evidence and attention regarding the cardio-protective role of Omega 3 fatty acids (n-3 PUFA) became progressively clear and appealing.

Epidemiological studies and randomized controlled trials confirms the role of n-3 PUFA in reducing all cause mortality and cardiovascular events mostly in patients at high cardiovascular risk. These effects seems to be mediated mostly by an anti-arrhythmogenic effect.

Basic science confirms and extended clinical observations regarding the antiarrhythmogenic effect of these compounds. Recently both basic research and clinical science suggested a role of n-3 PUFA for the prevention and treatment of supraventricular arrhythmias, particularly AF.

The purpose of the study is to show that the addition of n-3 PUFA on the top of the best recommended therapies can improve the maintenance of normal sinus rhythm in patients with persistent atrial fibrillation.

Eligibility criteria: Inclusion Criteria:

* Persistent atrial fibrillation

Exclusion Criteria:

* Contraindications or known hypersensitivity to n-3 PUFA
* Current treatment with n-3 PUFA for any reason
* Heart failure NYHA class IV
* Coronary artery bypass surgery or valve replacement within the past 3 months
* Planned cardiac procedures
* Known sick-sinus syndrome
* Diagnosis of Wolff-Parkinson-White
* Clinical significant valvular etiologies
* Presence of arrhythmia associated with an acute reversible condition
* Advanced chronic lung disease
* Contraindications for anticoagulation therapy
* Pregnancy or lactation
* Any non cardiac illness associated with a life expectancy of \< 2 years
* Treatment with any investigational agent within 3 month before randomization
* Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol

Primary outcomes:
measure: Survival free of atrial fibrillation
timeFrame: 12 months
Secondary outcomes:
measure: Number of patients in sinus rhythm at the time of each study visit
timeFrame: 12 months
measure: Number of hospitalizations for CV reasons
timeFrame: 12 months
measure: Number of all-cause hospitalizations
timeFrame: 12 months
measure: Incidence of TE events
timeFrame: 12 months
measure: Number of patients who die or with non-fatal thromboembolic events
timeFrame: 12 months
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Hospital Alemán
state: Buenos Aires
city: Caba
country: Argentina
facility: Clinica Constituyentes
state: Buenos Aires
city: Caba
country: Argentina
facility: Complejo Medico Policial Churruca Visca
state: Buenos Aires
city: Caba
country: Argentina
facility: Fundacion Favaloro
state: Buenos Aires
city: Lanus
country: Argentina
facility: Hospital Evita Pueblo FEDITEC
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Clinica y Maternidad Colon
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Hospital Privado de la Comunidad
state: Buenos Aires
city: Rosario
country: Argentina
facility: Sanatorio Parque
state: Santa Fe
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: CEMIC (Centro de Educación Médica e Investigaciones Clinicas Norberto Quirno)
city: Cordoba
country: Argentina
facility: Clinica Romagosa
city: Corrientes
country: Argentina
facility: Hospital José de San Martín
city: Misiones
country: Argentina
facility: Sanatorio Integral IOT
city: Salta
country: Argentina
facility: Centro Cardiovascular Salta
Study officials:
affiliation: Fundacion GESICA
name: Hernan C Doval, MD
role: STUDY_CHAIR
affiliation: Mario Negri Institute
name: Gianni Tognoni, MD
role: STUDY_CHAIR
affiliation: Fundacion GESICA
name: Hugo Grancelli, MD
role: STUDY_DIRECTOR
affiliation: Fundacion GESICA
name: Sergio Varini, MD
role: STUDY_DIRECTOR
affiliation: Fundacion GESICA
name: Daniel Nul, MD
role: STUDY_DIRECTOR
affiliation: Fundacion GESICA
name: Alejandro Macchia, MD
role: STUDY_DIRECTOR
References:
citation: Macchia A, Grancelli H, Varini S, Nul D, Laffaye N, Mariani J, Ferrante D, Badra R, Figal J, Ramos S, Tognoni G, Doval HC; GESICA Investigators. Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) trial. J Am Coll Cardiol. 2013 Jan 29;61(4):463-468. doi: 10.1016/j.jacc.2012.11.021. Epub 2012 Dec 19.
citation: Macchia A, Varini S, Grancelli H, Nul D, Laffaye N, Ferrante D, Tognoni G, Doval HC; FORomegaARD investigators. The rationale and design of the FORomegaARD Trial: A randomized, double-blind, placebo-controlled, independent study to test the efficacy of n-3 PUFA for the maintenance of normal sinus rhythm in patients with previous atrial fibrillation. Am Heart J. 2009 Mar;157(3):423-7. doi: 10.1016/j.ahj.2008.10.027. Epub 2009 Jan 8.