■可溶性血栓调节蛋白是内皮病的标志,伊洛前列素可以改善内皮功能。在感染性休克患者中,高血浆可溶性血栓调节蛋白水平(>10ng/mL)与更坏的器官功能障碍和死亡率相关.
■评估伊洛前列素与安慰剂治疗对脓毒性休克和血浆可溶性血栓调节蛋白水平高于10ng/mL的患者器官衰竭严重程度的影响。
■这位调查员发起的,适应性,平行组,分层,双盲随机临床试验于2019年11月1日至2022年7月5日在丹麦的6家医院进行.该试验的最大样本量为380,仅对200名患者进行了90天的随访,对无效性进行了中期分析。总的来说,纳入了重症监护病房(ICU)中的279名患有感染性休克和内皮病的成年人。
■患者以1:1的比例随机接受隐匿性静脉输注伊洛前列素,1ng/kg/min(n=142),或安慰剂(n=137)72小时。
■主要结局是ICU中的平均每日序贯器官衰竭评估(SOFA)评分,根据试验中心和符合方案人群的基线SOFA评分进行校正。5个器官系统中每个器官系统的SOFA评分范围从0到4,评分越高表明功能障碍越严重(最大评分,20).次要结果包括7天时的严重不良反应和严重不良事件以及90天时的死亡率。
■在279名随机患者中,分析了278例的数据(中位[IQR]年龄,69[58-77]岁;男性171(62%),伊洛前列素组142例,安慰剂组136例。在计划的中期分析中,该试验因无效而停止。伊洛前列素组的平均[IQR]每日SOFA评分为10.6(6.4-14.8),安慰剂组为10.5(5.9-15.5)(调整后的平均差异,0.2[95%CI,-0.8至1.2];P=.70)。伊洛前列素组90天时的死亡率为57%(142个中的81个),安慰剂组为51%(136个中的70个)(调整后的相对风险,1.12[95%CI,0.91-1.40];P=0.33)。伊洛前列素组142例患者中有26例(18%)发生严重不良事件,安慰剂组136例患者中有20例(15%)发生严重不良事件(调整后的相对风险,1.25[95%CI,0.73-2.15];P=.52)。仅观察到1例严重不良反应。
■在这项针对ICU中患有感染性休克和严重内皮病的成年人的随机临床试验中,输注伊洛前列素,1ng/kg/min,与安慰剂相比,72小时的平均每日SOFA评分没有降低.在临床上,伊洛前列素的给药不太可能改善这些患者的预后.
■ClinicalTrials.gov标识符:NCT04123444。
UNASSIGNED: Soluble
thrombomodulin is a marker of endotheliopathy, and iloprost may improve endothelial function. In patients with septic shock, high plasma levels of soluble
thrombomodulin (>10 ng/mL) have been associated with worse organ dysfunction and mortality.
UNASSIGNED: To assess the effects of treatment with iloprost vs placebo on the severity of organ failure in patients with septic shock and plasma levels of soluble
thrombomodulin higher than 10 ng/mL.
UNASSIGNED: This investigator-initiated, adaptive, parallel group, stratified, double-blind randomized clinical trial was conducted between November 1, 2019, and July 5, 2022, at 6 hospitals in Denmark. The trial had a maximum sample size of 380, with an interim analysis for futility only at 200 patients with 90 days of follow-up. In total, 279 adults in the intensive care unit (ICU) with septic shock and endotheliopathy were included.
UNASSIGNED: Patients were randomized 1:1 to masked intravenous infusion of iloprost, 1 ng/kg/min (n = 142), or placebo (n = 137) for 72 hours.
UNASSIGNED: The primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score in the ICU adjusted for trial site and baseline SOFA score for the per-protocol population. SOFA scores for each of the 5 organ systems ranged from 0 to 4, with higher scores indicating more severe dysfunction (maximum score, 20). The secondary outcomes included serious adverse reactions and serious adverse events at 7 days and mortality at 90 days.
UNASSIGNED: Of 279 randomized patients, data from 278 were analyzed (median [IQR] age, 69 [58-77] years; 171 (62%) male), 142 in the iloprost group and 136 in the placebo group. The trial was stopped for futility at the planned interim analysis. The mean [IQR] daily SOFA score was 10.6 (6.4-14.8) in the iloprost group and 10.5 (5.9-15.5) in the placebo group (adjusted mean difference, 0.2 [95% CI, -0.8 to 1.2]; P = .70). Mortality at 90 days in the iloprost group was 57% (81 of 142) vs 51% (70 of 136) in the placebo group (adjusted relative risk, 1.12 [95% CI, 0.91-1.40]; P = .33). Serious adverse events occurred in 26 of 142 patients (18%) for the iloprost group vs 20 of 136 patients (15%) for the placebo group (adjusted relative risk, 1.25 [95% CI, 0.73-2.15]; P = .52). Only 1 serious adverse reaction was observed.
UNASSIGNED: In this randomized clinical trial of adults in the ICU with septic shock and severe endotheliopathy, infusion of iloprost, 1 ng/kg/min, for 72 hours did not reduce mean daily SOFA scores compared with placebo. In a clinical context, administration of iloprost will be unlikely to improve outcome in these patients.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT04123444.