Results from the REPAIR Study Final Analysis: Effects of Macitentan on Right Ventricular (RV) Remodelling in Pulmonary Arterial Hypertension (PAH)

Abstract

To evaluate the effect of macitentan on RV and hemodynamic properties in PAH patients. REPAIR (NCT02310672) was a 52-week, open-label, single-arm, multicentre study evaluating the effect of macitentan on cardiopulmonary hemodynamics, RV remodelling and function. Primary endpoints were change from baseline (BL) to Week26 in RV stroke volume (RVSV), determined by cardiac MRI; and pulmonary vascular resistance (PVR), determined by right heart catheterization. Secondary endpoints included change from BL to Week 26 in MRI RV cavity volumes and myocardial mass, 6-minute walk distance (6MWD) and WHO functional class (FC). Macitentan 10mg was initiated in treatment-naïve patients, in patients receiving stable background phosphodiesterase type-5 inhibitor [PDE-5i] at BL, or in initial combination with PDE-5i. At a pre-specified interim analysis in 42 patients, both primary endpoints were met. Final supportive analyses included 71 patients with BL and post-BL data for both primary endpoints (modified Full Analysis Set; mFAS). Safety was assessed up to end of study treatment + 30 days in all patients who received ≥1 dose of macitentan (N=87). In the mFAS at BL, mean (SD) age was 45.2 (13.4) years, 57 (80.3%) patients were female, and most patients were FC II (34; 47.9%) and FC III (36; 50.7%); macitentan was initiated as monotherapy in 17(23.9%) patients, on top of stable background PDE-5i therapy in 27 (38.0%) patients and simultaneously with a PDE-5i in 27 (38.0%) patients. RVSV increased by 12 mL and PVR decreased by 38% from BL at Week26 (Table). Meaningful improvements in MRI and 6MWD secondary endpoints were also observed (Table). At Week26, WHO FC (N=71) improved in 40 (56.3%) and was unchanged in 30 (42.3%) patients; none worsened, 1 had missing data. The most common adverse events were peripheral oedema (21.8%), headache (20.7%) and dizziness (13.8%). REPAIR, the first multicentre study in PAH to use RVSV from cardiac MRI as a primary endpoint, showed significant, clinically-relevant improvements in RV function with macitentan as monotherapy or part of combination therapy. Safety was consistent with other macitentan clinical trial data.