采用低剂量或高剂量康复期血浆治疗重症 COVID-19 患者的标准治疗：一项多中心贝叶斯随机开放标签临床试验（COOP-COVID-19-MCTI）
Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI).
作者信息
Song Alice T W, Rocha Vanderson, Mendrone-Júnior Alfredo, Calado Rodrigo T, De Santis Gil C, Benites Bruno D, Costa-Lima Carolina, Vargas Taiani, Marques Leonardo S, Fernandes Juliana C, Breda Felipe C, Wendel Silvano, Fachini Roberta, Rizzo Luiz V, Kutner José Mauro, Avelino-Silva Vivian I, Machado Rafael R G, Durigon Edison L, Chevret Sylvie, Kallas Esper G
机构信息
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Fundação Pro Sangue Hemocentro de São Paulo, São Paulo, Brazil.
出版信息
Lancet Reg Health Am. 2022 Jun;10:100216. doi: 10.1016/j.lana.2022.100216. Epub 2022 Mar 15.
BACKGROUND
Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19.
METHODS
We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086.
FINDINGS
Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC ( = 42), Low-volume ( = 43) or High-volume ( = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion.
INTERPRETATION
In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits.
FUNDING
Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.
背景
输注康复期血浆可作为支持性治疗的辅助手段，以预防新冠病毒病（COVID-19）病情进展和死亡。我们旨在评估两剂高抗体滴度静脉注射康复期血浆（CP）治疗重症COVID-19的疗效和安全性。
方法
我们在巴西7家医院开展了一项贝叶斯随机开放标签多中心对照临床试验。症状出现10天内SARS-CoV2逆转录聚合酶链反应（RT-PCR）呈阳性且入院的成年人符合条件。患者被随机分配（1:1:1），分别单独接受标准治疗（SoC），或联合200毫升（150 - 300毫升）CP（低剂量组），或400毫升（300 - 600毫升）CP（高剂量组）；输注必须在随机分组后24小时内进行。随机分组采用集中式，按中心分层。主要结局是至第28天临床改善的时间，采用世界卫生组织十点量表进行测量，在意向性分析人群中进行评估。中期分析和最终分析均在贝叶斯框架下进行。该试验已在ClinicalTrials.gov注册：NCT04415086。
结果
2020年6月2日至2020年11月18日期间，129例患者入组并随机分配至SoC组（n = 42）、低剂量CP组（n = 43）或高剂量CP组（n = 44）。供体的中和抗体滴度中位数为1:320（四分位间距，1:160至1:1088）。未观察到康复期血浆有任何益处的证据，贝叶斯估计SoC组第28天临床改善率为72.7%（95%CI，58.8至84.7），而合并实验组为64.1%（95%CI, 53.8至73.7）（平均差异为-8.7%，95%CI，-24.6至8.2）。有1例与输血相关的皮肤轻度过敏反应，1例疑似输血相关急性肺损伤，但认为与康复期血浆输注无关。
解读
在这项针对成年重症COVID-19住院患者的前瞻性随机试验中，康复期血浆未显示出临床益处。
资助
巴西科学、技术和创新部，圣保罗州研究资助基金会。
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