The impact of torasemide on haemodynamic and neurohormonal stress, and cardiac remodelling in heart failure – TORNADO: a study protocol for a randomized controlled trial

Abstract

BackgroundApproximately 50% of heart failure patients are readmitted to hospital within 6 months, owing to deterioration of their condition. Thus, symptomatic treatment of heart failure requires significant improvement. The aim of this study is to compare the effects of torasemide and furosemide on biochemical parameters of haemodynamic and neurohormonal compensation, myocardial remodelling, clinical outcomes and quality of life in patients with chronic heart failure.MethodsThis is a multicentre, randomized, open, blinded endpoint phase-IV trial. The study includes 120 heart failure patients in NYHA (New York Heart Association) functional class II–IV, treated with optimal heart failure therapy, with indications for use of loop diuretics. At enrolment, patients are stable, with a fixed dose of loop diuretics. Patients are randomized to treatment with furosemide or torasemide (randomization 1:1). After randomization, the current fixed dose of furosemide is continued or is replaced by an equipotential dose of torasemide (4:1). The study consists of two control visits (3 and 6 months after enrolment) with minimal follow-up of 6 months. Assessment involves clinical examination, Quality of Life Questionnaire, laboratory tests, echocardiography, electrocardiography, 24 h Holter-electrocardiography monitoring, 6 -min walk test and assessment of fluid retention. Any need for dose adjustment is assessed during the observation. The primary objective is to compare the effects of torasemide and furosemide on clinical and biochemical parameters of haemodynamic and neurohormonal compensation and myocardial remodelling. Secondary objectives include monitoring of: changes in signs and symptoms of heart failure, NYHA functional class, quality of life, dosage changes, rate of readmissions and mortality.DiscussionDespite decades of the diuretic’s history, knowledge about diuretic therapy is still unsatisfactory. The most widely used diuretic, furosemide, has a stormy pharmacokinetics and pharmacodynamics, and is associated with a high risk of mortality and hospitalization for worsening heart failure. Reports are very encouraging and suggest beneficial effects of torasemide. Hence, there is a need for further studies of the overall effect of torasemide, compared with furosemide. This can translate into improved quality of life and better prognosis of patients with heart failure.Trial registrationClinicalTrials.gov, NCT01942109. Registered on 24 August 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1760-z) contains supplementary material, which is available to authorized users.

Comparative effectiveness of torasemide versus furosemide in symptomatic therapy in heart failure patients: Preliminary results from the randomized TORNADO trial

“…The preferential use of torsemide in these circumstances may be related to torasemide's smaller inter-and intraindividual variation in bioavailability, longer action increased bioavailability, longer half-life and maintained absorption in the setting of intestinal edema [6,21,22]. Moreover, diuretic therapy with torasemide instead of furosemide optimizes the quality of daily life of patients with HF by reducing number of mictions at 3, 6 and 12 h after diuretic intake, and urgency to urinate [6,13,22]. Other studies have also demonstrated improvement in sympathetic nerve activity as well as decreased left ventricle volumes and levels of BNP with torsemide compared to furosemide therapy [23,24].…”

“…The study was approved by a local ethical review board and an informed consent was obtained from each patient. The detailed methods and description of the study design have been described previously [13]. Briefly, the study included patients who were hospitalized in years 2015-2018 in two cardiology centers in Poland, including academic center and a district hospital.…”

Comparative Analysis of Long-Term Outcomes of Torasemide and Furosemide in Heart Failure Patients in Heart Failure Registries of the European Society of Cardiology

“…The antialdosterone action of torasemide may explain its ability to improve prognosis in HF patients. The TORasemide oN hemodynAmic and neurohormonal stress, and carDiac remOdelling in heart failure (TORNADO, NCT01942109), is an ongoing randomised clinical trial, may provide insight in this as it aims to assess the favourable effects of torasemide on biochemical and clinical parameters, and its effectiveness versus furosemide in improving cardiac remodelling and haemodynamic and neurohormonal stress in patients with HF [30].…”