Søe-Jensen Peter, Clausen Niels E, Bestle Morten H, Andersen Lars P K, Lange Theis, Johansson Pär I, Stensballe Jakob
Department of Anaesthesia and Intensive Care, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark.
Department of Anaesthesia and Intensive Care, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Acta Anaesthesiol Scand. 2025 Jan;69(1):e14565. doi: 10.1111/aas.14565.
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.
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.
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.
急性呼吸衰竭（ARF）在危重症患者中很常见，重症监护病房中50%的患者需要机械通气[3,4]。新型冠状病毒肺炎（COVID-19）大流行表明，COVID-19感染可导致微血管肺内皮损伤引起ARF。在一项随机临床试验中，将可溶性血栓调节蛋白（sTM）≥4 ng/mL定义为患有严重内皮病变的机械通气COVID-19患者随机分组，以评估72小时输注低剂量前列环素1 ng/kg/min或安慰剂的效果。前列环素组和安慰剂组的28天死亡率分别为21.9%和43.6%（风险比0.50；可信区间0.24至0.96，p = 0.06）。本试验的目的是研究前列环素的这种有益效果和安全性是否也存在于任何需要机械通气且伴有严重内皮病变的疑似肺部感染患者中。
这是一项多中心、随机、双盲、临床研究者发起的3期试验，研究对象为机械通气的疑似肺部感染且伴有严重内皮病变（定义为sTM≥4 ng/mL）的患者。患者按1:1随机分为两组，分别接受72小时输注低剂量前列环素（依洛前列素）1 ng/kg/min或安慰剂（等体积生理盐水）。将纳入450例患者。主要终点是28天全因死亡率。次要终点包括90天死亡率、28天和90天内在重症监护病房（ICU）无血管升压药、机械通气和肾脏替代治疗的存活天数，以及前7天内严重不良反应或严重不良事件的数量。
本试验将研究在机械通气的、任何疑似肺部感染且伴有严重内皮病变（定义为sTM≥4 ng/mL）的患者中，前列环素与安慰剂相比72小时的疗效和安全性。试验终点聚焦于前列环素降低28天全因死亡率的潜在效果。
