Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients - A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study

Circ J. 2020 Sep 25;84(10):1866-1874. doi: 10.1253/circj.CJ-20-0438. Epub 2020 Sep 3.

Abstract

Background: Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).

Methods and results: This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index.

Conclusions: Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).

Keywords: Chronic thromboembolic pulmonary hypertension; Prostacyclin receptor agonist; Pulmonary hemodynamics; Safety; Selexipag.

Publication types

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

MeSH terms

  • Acetamides / adverse effects*
  • Adult
  • Aged
  • Antihypertensive Agents / adverse effects*
  • Chronic Disease
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension, Pulmonary / complications*
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / epidemiology
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Prognosis
  • Pulmonary Embolism / complications*
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / epidemiology
  • Pyrazines / adverse effects*
  • Receptors, Epoprostenol / agonists
  • Treatment Outcome
  • Vascular Resistance / drug effects

Substances

  • Acetamides
  • Antihypertensive Agents
  • Pyrazines
  • Receptors, Epoprostenol
  • selexipag