Efficacy and safety of selexipag in patients with inoperable or persistent/recurrent CTEPH (SELECT randomised trial).

Abstract

BACKGROUND SELECT was the first global randomised controlled trial of selexipag with standard of care in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension. METHODS SELECT was a multicentre, randomised, double-blind, placebo-controlled, parallel-group, group-sequential, phase 3 study (NCT03689244). Adults aged ≤85 years in WHO functional class I-IV, with a 6-minute walk distance (6 MWD) of 100-450 m, were randomised (1:1) to receive selexipag (200-1600 µg b.i.d. titration until individual maximum tolerated dose)+standard of care or placebo+standard of care. Patients were recruited into the haemodynamic set (first 91 randomised patients to undergo right heart catheterisation [RHC]; Week 20) or non-haemodynamic cohort (remaining patients, no RHC required). Primary endpoint was percent of baseline pulmonary vascular resistance (PVR; Week 20). Safety was also assessed. RESULTS Of 321 patients screened, 128 were randomised (haemodynamic set: n=91 [selexipag: n=47; placebo: n=44]). In the haemodynamic set, 29 (31.9%) patients had previous pulmonary endarterectomy (PEA), 20 (22.0%) balloon pulmonary angioplasty (BPA), and 14 (15.4%) both PEA and BPA; 28 (30.8%) were inoperable. The Independent Data Monitoring Committee recommended to stop the study for futility as no statistically significant difference was observed for the primary endpoint (between-treatment geometric least squares mean ratio of PVR: 0.95 [95% CI 0.84, 1.07; p=0.412]). Adverse events were reported in 63 (98.4%) and 53 (82.8%) patients for selexipag and placebo, respectively. CONCLUSION SELECT was discontinued for futility, as no treatment effect on the primary endpoint (PVR) was observed. Safety data were consistent with the established safety profile of selexipag, with no new safety signals identified.