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吸入曲前列尼尔治疗间质性肺疾病所致肺动脉高压
Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease


Aaron Waxman ... 呼吸系统疾病 • 2021.01.28
相关阅读
• 通过吸入曲前列尼尔提高运动能力

摘要


背景

间质性肺疾病患者的肺动脉高压目前尚无获得批准的治疗方法。此类患者吸入曲前列尼尔的安全性和疗效尚不明确。

 

方法

在一项为期16周的多中心、随机、双盲、安慰剂对照试验中,我们纳入了间质性肺疾病合并肺动脉高压(通过右心导管检查证实)的患者。我们以1∶1的比例将患者随机分组,两组分别吸入曲前列尼尔(采用超声脉冲雾化器给药,每日4次,每次最多12吸[总共72 μg])或安慰剂。主要疗效终点是从基线至第16周,血浆药物水平峰值时6分钟步行距离(下文简称峰值6分钟步行距离)所发生变化的组间差异。次要终点包括第16周时氨基末端B型利尿钠肽前体(NT-proBNP)水平的变化和至临床状况恶化的时间。

 

结果

共计326例患者接受了随机分组,曲前列尼尔组163例,安慰剂组163例。两组的基线特征相似。第16周时,在曲前列尼尔组和安慰剂组之间,6分钟步行距离相对于基线的变化的最小二乘均值差异为31.12 m(95% CI,16.85~45.39;P<0.001)。曲前列尼尔组的NT-proBNP水平相对于基线降低了15%,而安慰剂组升高了46%(治疗比,0.58;95% CI,0.47~0.72;P<0.001)。曲前列尼尔组37例患者(22.7%)出现了临床状况恶化,而安慰剂组为54例患者(33.1%)(风险比,0.61;95% CI,0.40~0.92;时序检验的P=0.04)。最常报告的不良事件包括咳嗽、头痛、呼吸困难、眩晕、恶心、疲劳和腹泻。

 

结论

在间质性肺疾病导致的肺动脉高压患者中,与安慰剂相比,吸入曲前列尼尔提高了患者相对于基线的运动能力(采用6分钟步行试验进行评估)(由美国联合治疗公司[United Therapeutics]资助,INCREASE在ClinicalTrials.gov注册号为NCT02630316)。





作者信息

Aaron Waxman, M.D., Ph.D., Ricardo Restrepo-Jaramillo, M.D., Thenappan Thenappan, M.D., Ashwin Ravichandran, M.D., Peter Engel, M.D., Abubakr Bajwa, M.D., Roblee Allen, M.D., Jeremy Feldman, M.D., Rahul Argula, M.D., Peter Smith, Pharm.D., Kristan Rollins, Pharm.D., Chunqin Deng, M.D., Ph.D., Leigh Peterson, Ph.D., Heidi Bell, M.D., Victor Tapson, M.D., and Steven D. Nathan, M.D.
From Brigham and Women’s Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent’s Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) — both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars–Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.). Address reprint requests to Dr. Nathan at the Advanced Lung Disease and Lung Transplant Program, Inova Heart and Vascular Institute, 3300 Gallows Rd., Falls Church, VA 22042, or at steven.nathan@inova.org.

 

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