Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients Receiving Background Endothelin Receptor Antagonist and Phosphodiesterase Type 5 Inhibitor Therapy (The FREEDOM-C2 Study) A Randomized Controlled Trial
Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients Receiving Background Endothelin Receptor Antagonist and Phosphodiesterase Type 5 Inhibitor Therapy (The FREEDOM-C2 Study) A Randomized Controlled Trial
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DOI：
10.1378/chest.12-2875
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发表时间：
2013-09-01
期刊：
影响因子：
9.6
通讯作者：
Rubin, Lewis J.
中科院分区：
文献类型：
--
作者：
Tapson, Victor F.;Jing, Zhi-Cheng;Rubin, Lewis J.
背景资料：曲前列环素是一种稳定的前列环素类似物，批准用于治疗肺动脉高压（PAH），作为胃肠外或吸入治疗。对曲前列环素二醇胺（一种曲前列环素的缓释口服制剂）进行了研究，以确定其是否可以为重度程度较轻的PAH患者提供更方便的前列环素治疗选择。本研究的目的是评价口服曲前列尼尔在接受稳定背景内皮素受体拮抗剂（ERA）、磷酸二酯酶5型抑制剂（PDE-5I）治疗或两者联合治疗的PAH患者中的疗效和安全性。一项为期16周的多中心、双盲、一项在310例PAH患者中进行的安慰剂对照研究，比较了口服曲前列尼尔（n = 157）与安慰剂（n = 153）的bid给药。主要终点是第16周时6分钟步行距离的变化。次要疗效终点为世界卫生组织功能分级、博格呼吸困难评分、呼吸困难疲劳指数、PAH体征和症状以及临床恶化。结果：132例（84%）接受口服曲前列尼尔的患者和138例（90%）接受安慰剂的患者完成了研究。第16周口服曲前列尼尔的平均+/- SD剂量为3.1 +/- 1.9 mg bid。第16周时，Hodges-Lehmann安慰剂校正的6 MWD中位差异为10.0 m（95% CI，2.2 - 22 m; P = .089）。次要终点无显著变化。与口服曲前列尼尔相关的最常见的不良事件是头痛（71%）、腹泻（55%）、恶心（46%）、潮红（35%）和颌痛（25%）。结论：将口服曲前列尼尔添加到背景ERA和PDE-5I治疗中不会导致运动能力的统计学显著改善。副作用很常见，但大多数受试者都能耐受。
Background: Treprostinil is a stable prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) as parenteral or inhaled therapy. Treprostinil diolamine, a sustained-release oral formulation of treprostinil, was studied to determine whether it could provide a more convenient prostacyclin treatment option for patients with less severe PAH. The objective of this study was to evaluate the efficacy and safety of oral treprostinil in patients with PAH receiving stable background endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE-5I) therapy, or both.Methods: A 16-week, multicenter, double-blind, placebo-controlled study in 310 patients with PAH compared bid administration of oral treprostinil (n = 157) with placebo (n = 153). The primary end point was change in 6-min walk distance at week 16. Secondary efficacy end points were World Health Organization functional class, Borg dyspnea score, dyspnea-fatigue index, signs and symptoms of PAH, and clinical worsening.Results: One hundred thirty-two patients (84%) receiving oral treprostinil and 138 (90%) receiving placebo completed the study. The mean +/- SD dose of oral treprostinil at week 16 was 3.1 +/- 1.9 mg bid. The Hodges-Lehmann placebo-corrected median difference in 6MWD at week 16 was 10.0 m (95% CI, 2 2 to 22 m; P = .089). There were no significant changes in secondary end points. The most common adverse events associated with oral treprostinil were headache (71%), diarrhea (55%), nausea (46%), flushing (35%), and jaw pain (25%).Conclusions: The addition of oral treprostinil to background ERA and PDE-5I therapy did not result in a statistically significant improvement in exercise capacity. Side effects were common but tolerated by most subjects.