Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial.
Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial.
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DOI：
10.1016/j.ahj.2017.01.011
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发表时间：
2017-04
影响因子：
4.8
通讯作者：
Lahm T
中科院分区：
文献类型：
--
作者：
Kline JA;Hall CL;Jones AE;Puskarich MA;Mastouri RA;Lahm T
本研究假设，吸入NO加氧气治疗次大面积肺栓塞（PE）受试者将改善RV收缩功能;减少RV应变和坏死，同时改善患者呼吸困难，优于单独使用氧气治疗。本文描述了一项已注册（NCT 01939301）的原理和方案，这是一项即将完成的II期、三中心、随机、双盲、对照试验。符合条件的患者患有肺部影像学证实的急性PE。受试者必须血压正常，超声心动图显示RV功能障碍或肌钙蛋白或脑钠肽升高，且无纤溶药物。受试者接受NO加氧气或安慰剂治疗24小时（±3小时），在治疗前后采集血样，并在治疗后进行强制性超声心动图和高敏肌钙蛋白检查，以评估复合主要终点。N=78的样本量是基于24小时超声心动图显示高敏感性肌钙蛋白（<14 pg/mL）正常且RV正常的NO治疗患者增加30%，α=0.05，β=0.20。通过连续分光光度法监测高铁血红蛋白血症%和预先确定的方案来应对病情的紧急变化，以确保安全性。通过相同的罐、软件和器械显示器的物理屏蔽以及临床护理团队的查询来确保设盲，以评估设盲有效性。我们在31个月内招募了78名患者。没有病人已经退出停止作为一个安全问题的结果，没有病人有一个严重的不良事件相关的NO。我们目前的方法和协议的第一个双盲，随机试验吸入NO治疗PE。
The study hypothesis is that administration of inhaled NO plus oxygen to subjects with submassive pulmonary embolism (PE) will improve RV systolic function; reduce RV strain and necrosis while improving patient dyspnea more than treatment with oxygen alone. This paper describes the rationale and protocol for a registered (NCT01939301), a nearly completed Phase II, three-center, randomized, double blind, controlled trial. Eligible patients have pulmonary imaging-proven acute PE. Subjects must be normotensive, have RV dysfunction on echocardiography or elevated troponin or brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen or placebo for 24 hours (±3 h) with blood sampling before and after treatment, and mandatory echocardiography and high sensitivity troponin post treatment to assess the composite primary endpoint. The sample size of N=78 was predicated on 30% more NO-treated patients having a normal high sensitivity troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with α=0.05 and β=0.20. Safety was ensured by continuous spectrophotometric monitoring of %methemoglobinemia, and a predefined protocol to respond to emergent changes in condition. Blinding was ensured by identical tanks, software and physical shielding of the device display and query of the clinical care team to assess blinding efficacy. We have enrolled 78 patients over a 31 month period. No patient has been withdrawn stopped as a result of a safety concern, and no patient has had a serious adverse event related to NO. We present methods and a protocol for the first double-blinded, randomized trial of inhaled NO to treat PE.