TORAFIC study protocol: torasemide prolonged release versus furosemide in patients with chronic heart failure

Abstract

Loop diuretics, such as torasemide and furosemide, are important agents in the treatment of chronic heart failure. Beneficial effects of torasemide immediate-release formulation beyond diuresis have been documented as the ability of this compound to inhibit myocardial synthesis and deposition of collagen type I in patients with chronic heart failure. In addition, torasemide-treated patients, but not furosemide-treated patients, showed decreased serum concentrations of the C-terminal propeptide of procollagen type I, a biochemical marker of myocardial fibrosis. The aim of the TORAFIC study is to test the efficacy of torasemide prolonged-release formulation (PR) in reducing myocardial fibrosis in chronic heart failure in a large, randomized clinical trial. METHODS: This prospective, Phase IV, randomized, blinded end point, active-controlled clinical trial will randomize 142 patients with chronic heart failure in New York Heart Association functional class II-IV to 8 months treatment with either torasemide-PR (10-40 mg daily) or furosemide (40-160 mg daily). The primary objective is to test the hypothesis that torasemide-PR is superior to furosemide in reducing myocardial fibrosis. The primary outcome measure is the difference in the change of serum propeptide of procollagen type I concentration from the initial to the final visit between both study groups. Secondary outcome measures include all efficacy variables related to heart failure (signs and symptoms, ECG, echocardiogram and serum levels of N-terminal brain natriuretic propeptide). Secondary safety variables are heart rate, blood pressure, laboratory data, adverse events, cardiovascular events (hospital admission, emergency department visits) and quality of life (Minnesota questionnaire). DISCUSSION: This trial will test whether torasemide-PR possesses antifibrotic properties, which may provide an additional benefit beyond diuresis in patients with chronic heart failure.