Randomized investigation of the MitraClip device in heart failure: Design and rationale of the RESHAPE-HF2 trial design.

ABSTRACT

AIMS: The safety and effectiveness of the MitraClip device to treat functional mitral regurgitation (FMR) has been tested in previous clinical trials yielding somewhat heterogeneous results in heart failure (HF) patients. Over time, the MitraClip device system has been modified and clinical practice evolved to consider also less severely diseased HF patients with FMR for this therapeutic option. The RESHAPE-HF2 trial aims to assess the safety and effectiveness of the MitraClip device system on top of medical therapy considered optimal in the treatment of clinically significant FMR in symptomatic patients with chronic HF. METHODS: The RESHAPE-HF2 is an investigator-initiated, prospective, randomized, parallel-controlled, multicentre trial designed to evaluate the use of the MitraClip device (used in the most up-to-date version as available at sites) plus optimal standard of care therapy (device group) compared to optimal standard of care therapy alone (control group). Eligible subjects have signs and symptoms of HF (New York Heart Association [NYHA] class II-IV despite optimal therapy), and have moderate-to-severe or severe FMR, as confirmed by a central echocardiography core laboratory; have an ejection fraction between ≥20% and ≤50% (initially 15-35% for NYHA class II patients, and 15-45% for NYHA class III/IV patients); have been adequately treated per applicable standards, and have received appropriate revascularization and cardiac resynchronization therapy, if eligible; had a HF hospitalization or elevated natriuretic peptides (B-type natriuretic peptide [BNP] ≥300 pg/ml or N-terminal proBNP ≥1000 pg/ml) in the last 90 days; and in whom isolated mitral valve surgery is not a recommended treatment option. The trial has three primary endpoints, which are these (i) the composite rate of total (first and recurrent) HF hospitalizations and cardiovascular death during 24 months of follow-up, (ii) the rate of total (i.e. first and recurrent) HF hospitalizations within 24 months, and (iii) the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire overall score. The three primary endpoints will be analysed using the Hochberg procedure to control the familywise type I error rate across the three hypotheses. CONCLUSIONS: The RESHAPE-HF2 trial will provide sound evidence on the MitraClip device and its effects in HF patients with FMR. The recruitment was recently completed with 506 randomized patients.