A multicenter, randomized, double-blind, controlled study to evaluate the efficacy and safety of dantrolene on ventricular arrhythmia as well as mortality and morbidity in patients with chronic heart failure (SHO-IN trial): rationale and design

Abstract Background Leakage of Ca2+ from the sarcoplasmic reticulum (SR) is a critical contributing factor to heart failure pathophysiology. Therefore, reducing SR Ca2+ leaks may provide significant additive benefits when used in combination with conventional therapies. Dantrolene, a drug routinely used to treat malignant hyperthermia, also stabilizes the cardiac isoform of the release channel (RyR2), thus decreasing SR Ca2+ leaks. The purpose of this study is to evaluate the effect of chronic administration of dantrolene on heart failure and lethal arrhythmia in patients with chronic heart failure and reduced ejection fraction in a multicenter, randomized, double-blind, controlled study. Methods Patients with chronic heart failure who had functional status of New York Heart Association class II and III and a left ventricular ejection fraction Results This paper presents the rationale and trial design of the study. Recruitment for the study started on 8 December 2017. Conclusions The results of this trial will clarify the efficacy and safety of dantrolene for ventricular arrhythmia, as well as mortality and morbidity in patients with chronic heart failure and reduced ejection fraction during guideline-directed medical treatment.