Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension - A double-blind, randomized, placebo-controlled trial
Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension - A double-blind, randomized, placebo-controlled trial
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DOI：
10.1164/ajrccm.165.6.2106079
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发表时间：
2002-03-15
影响因子：
24.7
通讯作者：
Rubin, LJ
中科院分区：
文献类型：
--
作者：
Simonneau, G;Barst, RJ;Rubin, LJ
肺动脉高压是一种危及生命的疾病，持续静脉注射前列环素已被证明是有效的。然而，这种治疗需要永久性中心静脉导管，存在严重并发症的相关风险，如败血症、血栓栓塞或晕厥。曲前列环素是一种稳定的前列环素类似物，可以通过连续皮下输注给药，避免这些风险。我们在470名肺动脉高压患者中进行了一项为期12周的双盲、安慰剂对照多中心试验，这些患者要么是原发性的，要么与结缔组织疾病或先天性体肺分流相关。曲前列尼尔组运动能力改善，安慰剂组无变化;治疗组间6分钟步行距离中位数差异为16 m（p = 0.006）。病情较重的患者运动能力的改善更大，并且与剂量相关，但与疾病病因无关。同时，曲前列尼尔显著改善了呼吸困难指数、肺动脉高压体征和症状以及血流动力学。曲前列尼尔最常见的副作用是输注部位疼痛（85%），导致8%的患者提前退出研究。曲前列尼尔治疗组的三名患者出现胃肠道出血。我们的结论是，长期皮下输注曲前列尼尔是一种有效的治疗肺动脉高压患者的安全性可以接受。
Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous prostacyclin has proven to be effective. However, this treatment requires a permanent central venous catheter with the associated risk of serious complications such as sepsis, thromboembolism, or syncope. Treprostinil, a stable prostacyclin analogue, can be administered by a continuous subcutaneous infusion, avoiding these risks. We conducted a 12-week, double-blind, placebo-controlled multicenter trial in 470 patients with pulmonary arterial hypertension, either primary or associated with connective tissue disease or congenital systemic-to-pulmonary shunts. Exercise capacity improved with treprostinil and was unchanged with placebo; the between treatment group difference in median six-minute walking distance was 16 m (p = 0.006). Improvement in exercise capacity was greater in the sicker patients and was dose-related, but independent of disease etiology. Concomitantly, treprostinil significantly improved indices of dyspnea, signs and symptoms of pulmonary hypertension, and hemodynamics. The most common side effect attributed to treprostinil was infusion site pain (85%) leading to premature discontinuation from the study in 8% of patients. Three patients in the treprostinil treatment group presented with an episode of gastrointestinal hemorrhage. We conclude that chronic subcutaneous infusion of treprostinil is an effective treatment with an acceptable safety profile in patients with pulmonary arterial hypertension.