多中心随机、安慰剂对照、盲法、研究者发起的COMBAT-ARF试验方案:机械通气合并肺部感染和内皮病变患者输注72小时前列环素(1ng /kg/min)的有效性和安全性

IF 1.9 4区 医学 Q2 ANESTHESIOLOGY Acta Anaesthesiologica Scandinavica Pub Date : 2025-01-01 DOI:10.1111/aas.14565
Peter Søe-Jensen, Niels E Clausen, Morten H Bestle, Lars P K Andersen, Theis Lange, Pär I Johansson, Jakob Stensballe
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引用次数: 0

摘要

背景:急性呼吸衰竭(ARF)在重症患者中很常见,重症监护室中 50%的患者需要机械通气 [3,4]。COVID-19 大流行显示,COVID-19 感染诱发 ARF 的原因是微血管肺内皮受损。在一项随机临床试验中,机械通气的 COVID-19 患者因可溶性血栓调节蛋白(sTM)≥ 4 纳克/毫升而出现严重内皮病变,该试验随机评估了 72 小时输注小剂量前列环素 1 纳克/千克/分钟或安慰剂的效果。前列环素组和安慰剂组的二十八天死亡率分别为 21.9% 和 43.6%(RR 0.50;CI 0.24 至 0.96 p = .06)。当前试验的目的是研究前列环素的这种益处和安全性是否也适用于任何需要机械通气的疑似肺部感染并同时伴有严重内皮细胞病变的患者:这是一项多中心、随机、盲法、临床研究者发起的3期试验,对象是疑似肺部感染和严重内皮细胞病变(定义为sTM≥4 ng/mL)的机械通气患者。患者按 1:1 随机分配到输注低剂量前列环素(伊洛前列素)1 纳克/公斤/分钟或安慰剂(等量生理盐水)72 小时。共纳入 450 名患者。主要终点是 28 天的全因死亡率。次要终点包括 90 天死亡率、重症监护室 28 天和 90 天内无血管加压、机械通气和肾脏替代治疗的存活天数,以及头 7 天内严重不良反应或严重不良事件的数量:本试验将研究前列环素与安慰剂在任何疑似肺部感染和严重内皮细胞病变(定义为 sTM ≥4 纳克/毫升)的机械通气患者中使用 72 小时的疗效和安全性。试验终点侧重于前列环素降低 28 天全因死亡率的潜在效果。
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Efficacy and safety of a 72-h infusion of prostacyclin (1 ng/kg/min) in mechanically ventilated patients with pulmonary infection and endotheliopathy-protocol for the multicenter randomized, placebo-controlled, blinded, investigator-initiated COMBAT-ARF trial.

Background: Acute respiratory failure (ARF) is common in critically ill patients, and 50% of patients in intensive care units require mechanical ventilation [3, 4]. The COVID-19 pandemic revealed that COVID-19 infection induced ARF caused by damage to the microvascular pulmonary endothelium. In a randomized clinical trial, mechanically ventilated COVID-19 patients with severe endotheliopathy, as defined by soluble thrombomodulin (sTM) ≥ 4 ng/mL, were randomized to evaluate the effect of a 72-h infusion of low-dose prostacyclin 1 ng/kg/min or placebo. Twenty-eight-day mortality was 21.9% versus 43.6% in the prostacyclin and the placebo groups, respectively (RR 0.50; CI 0.24 to 0.96 p = .06). The aim of the current trial is to investigate if this beneficial effect and safety of prostacyclin also are present in any patient with suspected pulmonary infection requiring mechanical ventilation and concomitant severe endotheliopathy.

Materials and methods: This is a multi-center, randomized, blinded, clinical investigator-initiated phase 3 trial in mechanically ventilated patients with suspected pulmonary infection and severe endotheliopathy, as defined by sTM ≥4 ng/mL. Patients are randomized 1:1 to a 72-h infusion of low-dose prostacyclin (iloprost) 1 ng/kg/min or placebo (an equal volume of saline). Four-hundred fifty patients will be included. The primary endpoint is 28-day all-cause mortality. Secondary endpoints include 90-day mortality, days alive without vasopressor, mechanical ventilation, and renal replacement therapy in the ICU within 28 and 90 days, and the number of serious adverse reactions or serious adverse events within the first 7 days.

Discussion: This trial will investigate the efficacy and safety of prostacyclin vs. placebo for 72-hours in mechanically ventilated patients with any suspected pulmonary infection and severe endotheliopathy, as defined by sTM ≥4 ng/mL. Trial endpoints focus on the potential effect of prostacyclin to reduce 28-day all-cause mortality.

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来源期刊
CiteScore
4.30
自引率
9.50%
发文量
157
审稿时长
3-8 weeks
期刊介绍: Acta Anaesthesiologica Scandinavica publishes papers on original work in the fields of anaesthesiology, intensive care, pain, emergency medicine, and subjects related to their basic sciences, on condition that they are contributed exclusively to this Journal. Case reports and short communications may be considered for publication if of particular interest; also letters to the Editor, especially if related to already published material. The editorial board is free to discuss the publication of reviews on current topics, the choice of which, however, is the prerogative of the board. Every effort will be made by the Editors and selected experts to expedite a critical review of manuscripts in order to ensure rapid publication of papers of a high scientific standard.
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