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

Paweł Balsam, Krzysztof Ozierański, Agata Tymińska, Renata Główczyńska, Michał Peller, Anna Fojt, Andrzej Cacko, Bartosz Sieradzki, Elwira Bakuła, Maciej Markulis, Robert Kowalik, Zenon Huczek, Krzysztof J Filipiak, Grzegorz Opolski, Marcin Grabowski, Paweł Balsam, Krzysztof Ozierański, Agata Tymińska, Renata Główczyńska, Michał Peller, Anna Fojt, Andrzej Cacko, Bartosz Sieradzki, Elwira Bakuła, Maciej Markulis, Robert Kowalik, Zenon Huczek, Krzysztof J Filipiak, Grzegorz Opolski, Marcin Grabowski

Abstract

Background: Approximately 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.

Methods: This 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.

Discussion: Despite 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 registration: ClinicalTrials.gov, NCT01942109 . Registered on 24 August 2013.

Keywords: Dose; Furosemide; Heart failure; Hospitalization; Loop diuretic; Prognosis; Quality of life; Randomized controlled trial; Torasemide.

Figures

Fig. 1
Fig. 1
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)
Fig. 2
Fig. 2
Study design as flow diagram: recruitment, randomization, intervention, follow-up, assessment and outcomes. CHF, chronic heart failure; NYHA, New York Heart Association

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