The ongoing UNISUS hemodynamic sub-study enrolled 128 patients (mean age 48.7 years, 78.9% female) to evaluate macitentan 75 mg versus 10 mg on right heart function in pulmonary arterial hypertension.
RCT (n=128)
Double-blind, double-dummy
1:1
Yes
Does macitentan 75 mg improve time to first morbidity/mortality event and hemodynamics compared to macitentan 10 mg in adult patients with pulmonary arterial hypertension?
The UNISUS hemodynamic sub-study outlines the baseline characteristics of 128 PAH patients enrolled to evaluate the efficacy of high-dose (75 mg) versus standard-dose (10 mg) macitentan on right heart function.
Abstract Rationale In PAH, assessment of the right heart function by right heart catheterization (RHC) is critical to understanding treatment response. UNISUS, the first head-to-head superiority study in PAH, assesses the treatment effect of macitentan 75 mg and includes a hemodynamic sub-study. UNISUS will evaluate macitentan 75 mg (hypothesized to confer potent blockade of both endothelin ET A receptors and ETB receptors) versus macitentan 10 mg (potent ETA and partial ETB receptor blockade) in PAH, with time to first morbidity/mortality event as the primary endpoint. Here we describe the study design and preliminary baseline characteristics of patients included in the hemodynamic sub-study. Methods UNISUS (NCT04273945) is an ongoing phase 3, prospective, multicenter, double-blind, double-dummy, randomized, active-controlled, parallel-group, group-sequential, adaptive, event-driven superiority study in patients with PAH, randomized 1:1 to receive macitentan 75 mg or 10 mg once-daily. UNISUS enrolled adult PAH patients, in WHO functional class (FC) II-IV, with or without prior PAH treatment. The hemodynamic sub-study was conducted at selected sites based on their ability to perform RHC, experience with the procedure and willingness to participate. Patients underwent RHC at baseline and Week 24 to evaluate changes in key hemodynamic parameters, including pulmonary vascular resistance, mean right atrial pressure, mean pulmonary arterial pressure and cardiac index. Results The UNISUS hemodynamic sub-study includes 128 patients from 52 sites (Overall: 935 patients from 229 sites). Mean (SD) age was 48.7 years (16.8), 78.9% were female and median (Q1,Q3) time since diagnosis was 4.0 years (1.4, 7.7). Patients were from North-East Asia and Pacific (35.9%), Latin America (28.9%), Western Europe (12.5%), North America (10.9%), South-East Asia (6.3%) and Eastern Europe (5.5%). Idiopathic PAH accounted for 60.2% of patients, followed by PAH associated with connective tissue disease (21.1%) and PAH due to corrected or small/coincidental congenital heart disease (10.2%). Distribution of FC was 66.4% FC II and 33.6% FC III. Mean (SD) 6-minute walk distance was 367.3 m (70.2) and median (Q1,Q3) N-terminal pro-brain natriuretic peptide level was 231.0 ng/L (107.0, 664.0). At screening, 27.3% were receiving 1 PAH therapy and 71.9% ≥2 PAH therapies. Conclusions The UNISUS hemodynamic sub-study will provide critical insights into the effects of macitentan 75 mg on the right heart function in a diverse and broad PAH patient population. These findings may inform future therapeutic strategies by enhancing our understanding of the clinical impact of maximal dual ETA and ETB receptor inhibition in PAH. This abstract is funded by: Johnson & Johnson
Humbert et al. (Fri,) conducted a rct in Pulmonary Arterial Hypertension (PAH) (n=128). Macitentan vs. Macitentan 10 mg once-daily was evaluated on Time to first morbidity/mortality event. The ongoing UNISUS hemodynamic sub-study enrolled 128 patients (mean age 48.7 years, 78.9% female) to evaluate macitentan 75 mg versus 10 mg on right heart function in pulmonary arterial hypertension.