Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients on Background Endothelin Receptor Antagonist and/or Phosphodiesterase Type 5 Inhibitor Therapy (The FREEDOM-C Study) A Randomized Controlled Trial
Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients on Background Endothelin Receptor Antagonist and/or Phosphodiesterase Type 5 Inhibitor Therapy (The FREEDOM-C Study) A Randomized Controlled Trial
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DOI：
10.1378/chest.11-2212
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发表时间：
2012-12-01
期刊：
影响因子：
9.6
通讯作者：
Galie, Nazzareno
中科院分区：
文献类型：
--
作者：
Tapson, Victor E.;Torres, Fernando;Galie, Nazzareno
背景：输注和吸入曲前列环素可有效治疗肺动脉高压（PAH），但其给药途径有局限性。本研究评估了每日两次口服缓释曲前列环素联合内皮素受体拮抗剂 (ERA) 和/或 5 型磷酸二酯酶抑制剂治疗 PAH 的有效性和安全性。方法：在 350 名随机接受安慰剂或口服曲前列环素的 PAH 患者中进行了一项为期 16 周、多中心、双盲、安慰剂对照研究。所有患者在使用背景 ERA、PDE-5 抑制剂或两者均稳定的情况下。主要终点是第 16 周时 Hodges-Lehmann 安慰剂校正的与基线 6 分钟步行距离 (6MWD) 变化的中位差异。次要终点包括临床恶化时间、世界卫生组织功能分级变化、Borg 呼吸困难评分和呼吸困难疲劳指数评分。结果：39 名接受口服曲前列环素的患者 (22%) 和 24 名接受安慰剂的患者 (14%) 终止了研究。第 16 周时与基线 6MWD 变化的安慰剂校正中位数差异为 11 英寸 (P = .07)。与安慰剂治疗相比，口服曲前列环素治疗观察到呼吸困难疲劳指数评分 (P = .01) 以及 6MWD 和 Borg 呼吸困难评分 (P = .01) 的改善。 16 周 bid 口服曲前列环素剂量为 1.25 至 3.25 mg 和 3.5 至 16 mg 的患者的 6MWD 变化（分别为 18 m 和 34 m）比达到 bid 接近 < 1 mg 或因不良事件而停药的患者 (4 m) 更大。结论：第 16 周时 6MWD 改善的主要终点没有达到显着性。这项研究增强了对口服曲前列环素滴定和剂量的理解，为进一步的研究奠定了基础。试验注册：ClinicalTrials.gov；编号：NCT00325442；网址：www.clinicaltrials.gov CHEST 2012； 142(6):1383-1390
Background: Infused and inhaled treprostinil are effective for treatment of pulmonary arterial hypertension (PAH), although their administration routes have limitations. This study assessed the efficacy and safety of bid oral sustained-release treprostinil in the treatment of PAH with a concomitant endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor.Methods: A 16-week, multicenter, double-blind, placebo-controlled study was conducted in 350 patients with PAH randomized to placebo or oral treprostinil. All patients were stable on background ERA, PDE-5 inhibitor, or both. Primary end point was Hodges-Lehmann placebo-corrected median difference in change from baseline 6-min walk distance (6MWD) at week 16. Secondary end points included time to clinical worsening, change in World Health Organization functional class, Borg dyspnea score, and dyspnea fatigue index score.Results: Thirty-nine patients (22%) receiving oral treprostinil and 24 patients (14%) receiving placebo discontinued the study. Placebo-corrected median difference in change from baseline 6MWD at week 16 was 11 in (P = .07). Improvements in dyspnea fatigue index score (P = .01) and combined 6MWD and Borg dyspnea score (P = .01) were observed with oral treprostinil vs placebo treatment. Patients who achieved a week-16 bid oral treprostinil dose of 1.25 to 3.25 mg and 3.5 to 16 mg experienced a greater change in 6MWD (18 m and 34 m, respectively) than patients who achieved a bid close of < 1 mg or discontinued because of adverse events (4 m).Conclusions: The primary end point of improvement in 6MWD at week 16 did not achieve significance. This study enhanced understanding of oral treprostinil titration and dosing, which has set the stage for additional studies.Trial registry: ClinicalTrials.gov; No.: NCT00325442; URL: www.clinicaltrials.gov CHEST 2012; 142(6):1383-1390