Rationale and design of a randomised controlled clinical trial on supplemental intake of n-3 fatty acids and incidence of cardiac arrhythmia: SOFA

Background: Evidence from earlier studies indicates that intake of very long-chain n-3 polyunsaturated fatty acids (n-3 PUFA, also named omega-3 fatty acids) as present in fish oil reduces the risk of sudden death. Sudden death forms a major part of mortality from cardiovascular disease and is in most cases a direct consequence of cardiac arrhythmia. n-3 PUFA may exert their protective effect through reducing the susceptibility for cardiac arrhythmia. Objective: To investigate the effect of n-3 PUFA on the incidence of recurrent ventricular arrhythmia. This paper presents the rationale, design and methods of the Study on Omega-3 Fatty acids and ventricular Arrhythmia (SOFA) and discusses problems encountered in conducting a multicentre clinical trial on food. Design: A randomised, parallel, placebo-controlled, double blind intervention study, which obeys the guidelines for Good Clinical Practice. Setting: Multiple cardiology centres in Europe. Subjects: A total of 500 patients with an implantable cardioverter defibrillator (ICD). An ICD detects, treats and stores cardiac arrhythmic events in its memory chip. Interventions: Patients receive either 2 g/day of fish oil, containing approximately 450 mg eicosapentaenoic acid and 350 mg docosahexaenoic acid, or placebo for 12 months. Primary outcome: Spontaneous ventricular tachyarrhythmias as recorded by the ICD or all-cause mortality. Conclusion: SOFA is designed to answer the question whether intake of n-3 PUFA from fish-a regular food ingredient-can reduce the incidence of life-threatening cardiac arrhythmia. If this proves to be true, increasing the intake of n-3 PUFA could be an easy, effective and safe measure to prevent fatal arrhythmia in the general population