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

Eur Respir J. 2024 Oct 3;64(4):2400193. doi: 10.1183/13993003.00193-2024. Print 2024 Oct.

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 (ClinicalTrials.gov: NCT03689244). Adults aged ≤85 years in World Health Organization Functional Class I-IV, with a 6-min walk distance of 100-450 m, were randomised (1:1) to receive selexipag (200-1600 µg twice daily 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). The primary end-point 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 end-point (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.

Conclusions: SELECT was discontinued for futility, as no treatment effect on the primary end-point (PVR) was observed. Safety data were consistent with the established safety profile of selexipag, with no new safety signals identified.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Clinical Trial, Phase III

MeSH terms

  • Acetamides* / administration & dosage
  • Acetamides* / adverse effects
  • Acetamides* / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use
  • Cardiac Catheterization
  • Chronic Disease
  • Double-Blind Method
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hypertension, Pulmonary* / drug therapy
  • Male
  • Middle Aged
  • Pulmonary Embolism* / drug therapy
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use
  • Recurrence
  • Treatment Outcome
  • Vascular Resistance / drug effects

Substances

  • selexipag
  • Acetamides
  • Pyrazines
  • Antihypertensive Agents

Associated data

  • ClinicalTrials.gov/NCT03689244