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])

背景： Selexipag是具有非前列腺素结构的口服前列环素受体（IP受体）激动剂。这项研究检查了其在日本非手术或持续/复发性慢性血栓栓塞性肺动脉高压（CTEPH）患者中的疗效和安全性。

方法和结果：这项II期研究是一项随机，双盲，安慰剂对照的平行组比较。主要终点是从基线到第17周肺血管阻力（PVR）的变化。主要分析涉及按协议组的28位受试者。塞来昔帕组治疗17周后PVR的变化（平均值±SD）为-104±191 dyn·s / cm ⁵，而安慰剂组为26±180 dyn·s / cm ⁵。因此，计算出的selexipag治疗17周后的治疗效果为-130±189 dyn·s / cm ⁵（P ＝ 0.1553）。尽管未达到主要终点，但对于不同时使用肺血管扩张剂的组，与安慰剂组相比，selexipag组的PVR显着降低（P = 0.0364）。selexipag组的总肺阻力和心脏指数也有所改善。

结论： Selexipag治疗可改善日本CTEPH患者的肺血流动力学，但PVR在selexipag组和安慰剂组之间无显着差异。（试验注册：JAPIC临床试验信息[JapicCTI-111667]）