A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of immunosuppression in biopsy-proven virus-negative myocarditis or inflammatory cardiomyopathy (IMPROVE-MC)

Background: Myocarditis is frequently associated with poor prognosis as there is no evidence-based treatment. Therefore, current international recommendations indicate that a well-designed prospective trial to confirm benefits from immunosuppressive therapy is highly warranted. The aim of the IMPROVE-MC study is to assess the efficacy and safety of immunosuppressive treatment compared with placebo on top of the guideline-recommended medical therapy in patients with biopsy-proven virus-negative myocarditis/inflammatory cardiomyopathy. Methods : The IMPROVE-MC (ClinicalTrials.gov: NCT04654988) is a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that will recruit 100 adults, with biopsy-proven myocarditis/inflammatory cardiomyopathy, with left ventricular ejection fraction (LVEF) ≤ 45% and ≥ 3-month history of symptoms. Patients will be randomized (1:1 ratio) to a group treated with prednisone and azathioprine vs. placebo. Patients will undergo 1-year double-blind therapy followed by a 1-year observation period to assess the long-term effects of the treatment. Apart from a routine clinical work-up, all patients will undergo cardiac magnetic resonance (CMR) and biopsy during screening and 1 year after applying the therapy. Primary endpoint is a change from baseline in LVEF at 12 months. Secondary endpoints are related to clinical evaluation (including New York Heart Association class, distance in 6-minute walk test, number of patients with the need for hospitalization), laboratory findings (biomarkers of fibrosis and myocardial necrosis, concentration of anti-heart auto-antibodies, heart tissue immunohistologic assessment), diagnostic tools (e.g., changes of echocardiographic, CMR and Holter-ECG parameters) and quality of life. Conclusions: The IMPROVE-MC study will provide high-quality scientific data on the efficacy and safety of immunosuppressive therapy for patients with biopsy-proven myocarditis. Trial registration number and date of registration: ClinicalTrials.gov:NCT04654988; 04/12/2020