Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19 A Randomized Clinical Trial
Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19 A Randomized Clinical Trial
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DOI：
10.1001/jama.2020.10044
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发表时间：
2020-08-04
影响因子：
120.7
通讯作者：
Liu, Zhong
中科院分区：
文献类型：
--
作者：
Li, Ling;Zhang, Wei;Liu, Zhong
重要性恢复期血浆是冠状病毒病患者的潜在治疗选择2019目的评价恢复期血浆疗法治疗COVID-19患者的疗效和不良反应。设计、设置和参与者在中国武汉的7个医学中心进行的开放标签、多中心、随机临床试验。从2020年2月14日至2020年4月1日，最终随访时间为2020年4月28日。该试验包括103名实验室确诊的COVID-19严重（呼吸窘迫和/或低氧血症）或危及生命（休克、器官衰竭或需要机械通气）的参与者。在计划的200名患者中有103名入选后，试验提前终止。干预恢复期血浆加标准治疗（n = 52）vs仅标准治疗（对照）（n = 51），按疾病严重程度分层。主要结果和测量主要结果是28天内临床改善的时间，定义为患者存活出院或6分疾病严重程度量表降低2分（范围为1 [出院]至6 [死亡]）。次要结果包括28天死亡率、出院时间和病毒聚合酶链反应（PCR）结果从基线阳性到72小时内阴性的比率。结果在103例随机分组的患者中（中位年龄70岁; 60例[58.3%]男性），101例（98.1%）完成了试验。恢复期血浆组51.9%（27/52）的患者在28天内出现临床改善，对照组43.1%（22/51）的患者出现临床改善（差异：8.8% [95% CI，-10.4%至28.0%];风险比[HR]：1.40 [95% CI，0.79-2.49]; P = 0.26）。在严重疾病患者中，恢复期血浆组的主要结局发生率为91.3%（21/23），对照组为68.2%（15/22（HR，2.15 [95% CI，1.07-4.32]; P = .03）;在危及生命的疾病患者中，恢复期血浆组的主要结局发生率为20.7%（6/29），对照组为24.1%（7/29（HR，0.88 [95% CI，0.30-2.63]; P = .83）（相互作用P = .17）。28天死亡率（15.7% vs 24.0%; OR，0.59 [95% CI，0.22-1.59]; P = 0.30）或从随机化至出院的时间（51.0% vs 36.0%，第28天出院; HR，1.61 [95% CI，0.88-2.95]; P = 0.12）无显著差异。恢复期血浆治疗与72小时病毒PCR的阴转率相关，恢复期血浆组为87.2%，对照组为37.5%（OR，11.39 [95%CI，3.91-33.18]; P <0.001）。恢复期血浆治疗组的两名患者在输血后数小时内发生了不良事件，并在支持性护理下得到改善。结论和相关性在严重或危及生命的COVID-19患者中，与单独使用标准治疗相比，在标准治疗的基础上增加恢复期血浆治疗，在28天内临床改善的时间方面没有统计学显著改善。由于试验提前终止，解释受到限制，这可能不足以检测出临床上重要的差异。
Importance Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed.Objective To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19.Design, Setting, and Participants Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled.Intervention Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity.Main Outcomes and Measures Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours.Results Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care.Conclusion and Relevance Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.