Section of Allergy, Immunology and Rheumatology, Department of Pediatrics, CHU Sainte-Justine, Montreal, Quebec, Canada.
Department of Medicine, CHUM, Université de Montréal, Montreal, Quebec, Canada.
Trials. 2021 May 4;22(1):323. doi: 10.1186/s13063-021-05235-3.
Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection.
CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600).
This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification.
Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.
恢复期血浆已被用于治疗多种病毒性疾病，包括流感、严重急性呼吸综合征、中东呼吸综合征和埃博拉病毒；然而，支持其使用的证据是薄弱的。SARS-CoV-2 是一种新型冠状病毒，可导致 2019 年全球 COVID-19 社区获得性肺炎大流行。我们进行了一项随机对照试验，以评估 COVID-19 恢复期血浆（CCP）在 SARS-CoV-2 感染患者中的疗效和安全性。
CONCOR-1 是一项开放性、多中心、随机试验。纳入标准包括：年龄＞16 岁，因 COVID-19 感染住院，因 COVID-19 呼吸并发症需要补充氧气，且有血型相容的 CCP。排除标准为：发病症状早于随机分组 12 天以上，气管插管或即将进行气管插管，以及对血浆有过严重过敏反应。同意参加的患者以 2:1 的比例随机接受大约 500mL 的 CCP 或标准治疗。CCP 从已从 COVID-19 中康复且血清学检测到 SARS-CoV-2 抗体的供者中采集。主要结局是 30 天内插管或死亡。次要结局包括无呼吸机天数、重症监护或住院时间、输血反应、严重不良事件以及 SARS-CoV-2 病毒载量的减少。探索性分析包括接受高滴度抗体 CCP 的患者。假设基线 30 天插管或死亡风险为 30%（双侧检验；α=0.05），1200 例患者的样本量可检测到 25%的相对风险降低，具有 80%的效力。在达到目标入组人数的 50%（n=600）时，将由一名未设盲的独立生物统计学家对主要结局数据进行分析，并对样本量进行重新估计。
该试验将确定 CCP 是否会降低未插管的 COVID-19 成年患者的插管或死亡率。该试验还将提供有关 SARS-CoV-2 抗体滴度和中和测定在供者资格中的作用和阈值的信息。
Clinicaltrials.gov NCT04348656。于 2020 年 4 月 16 日注册。
