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恢复期血浆对 COVID-19 重症患者器官支持无依赖天数的影响:一项随机临床试验。

Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

机构信息

NHS Blood and Transplant, Oxford, England.

Radcliffe Department of Medicine and BRC Hematology Theme, University of Oxford, Oxford, England.

出版信息

JAMA. 2021 Nov 2;326(17):1690-1702. doi: 10.1001/jama.2021.18178.


DOI:10.1001/jama.2021.18178
PMID:34606578
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8491132/
Abstract

IMPORTANCE: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. OBJECTIVE: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONS: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURES: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group. CONCLUSIONS AND RELEVANCE: Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

摘要

重要性:关于恢复期血浆治疗 COVID-19 危重症患者的疗效证据尚无定论。

目的:确定恢复期血浆是否会改善 COVID-19 危重症成人的结局。

设计、地点和参与者:正在进行的社区获得性肺炎的随机、嵌入式、多因素、适应性平台试验(REMAP-CAP)纳入了 2020 年 3 月 9 日至 2021 年 1 月 18 日期间至少在一个领域疑似或确诊 COVID-19 的 4763 名成年人,并对他们进行了随机分组;2011 名危重症患者在 4 个国家的 129 个地点的免疫球蛋白领域被随机分配至开放标签干预组。随访于 2021 年 4 月 19 日结束。

干预措施:免疫球蛋白领域的随机分组参与者在随机分组后 48 小时内接受 2 单位高滴度、ABO 相容的恢复期血浆(总容量为 550 毫升±150 毫升)(n=1084)或不接受恢复期血浆(n=916)。

主要结局和测量指标:主要的序贯终点是器官支持无天数(从存活日到第 21 天,范围为-1 到 21 天;死亡患者被分配-1 天)。主要分析采用了调整后的贝叶斯累积逻辑模型。优势被定义为优势比(OR)大于 1(优势结论的阈值>99%)的后验概率。无效性被定义为 OR 小于 1.2(无效结论的阈值>95%)的后验概率。OR 大于 1 代表生存改善、更多的器官支持无天数或两者兼有。预先指定的次要结局包括院内生存率;28 天生存率;90 天生存率;无呼吸支持天数;无心血管支持天数;进展为有创机械通气、体外机械氧合或死亡;重症监护病房住院时间;住院时间;第 14 天世界卫生组织等级量表评分;90 天静脉血栓栓塞事件;以及严重不良事件。

结果:在随机分组的 2011 名参与者中(中位数年龄为 61 岁[IQR,52 至 70 岁],645/1998[32.3%]为女性),1990 名(99%)完成了试验。在达到无效性的既定标准后,停止了恢复期血浆干预。在恢复期血浆组中,器官支持无天数的中位数为 0(IQR,-1 至 16),在无恢复期血浆组中为 3(IQR,-1 至 16)。恢复期血浆组的院内死亡率为 37.3%(401/1075),无恢复期血浆组为 38.4%(347/904),分别存活且无器官支持的天数中位数为 14(IQR,3 至 18)和 14(IQR,7 至 18)。中位调整后的 OR 为 0.97(95%可信区间,0.83 至 1.15),且恢复期血浆组的无效后验概率(OR <1.2)为 99.4%。与无恢复期血浆组相比,恢复期血浆组的治疗效果在主要结局和 11 个次要结局中均一致。3.0%(32/1075)的恢复期血浆组和 1.3%(12/905)的无恢复期血浆组报告了严重不良事件。

结论和相关性:在确诊 COVID-19 的危重症成人中,使用 2 单位高滴度、ABO 相容的恢复期血浆治疗不太可能改善无器官支持天数。

试验注册:ClinicalTrials.gov 标识符:NCT02735707。

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