恢复期血浆治疗印度成人中度 COVID-19 的管理：开放标签 II 期多中心随机对照试验（PLACID 试验）。

Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial).

机构信息

Clinical Trial and Health Systems Research Unit, Indian Council of Medical Research, V Ramalingaswamy Bhawan, PO Box 4911, Ansari Nagar, New Delhi, 110029, India.

Clinical Trial and Health Systems Research Unit, Indian Council of Medical Research, V Ramalingaswamy Bhawan, PO Box 4911, Ansari Nagar, New Delhi, 110029, India

出版信息

BMJ. 2020 Oct 22;371:m3939. doi: 10.1136/bmj.m3939.

OBJECTIVE

To investigate the effectiveness of using convalescent plasma to treat moderate coronavirus disease 2019 (covid-19) in adults in India.

DESIGN

Open label, parallel arm, phase II, multicentre, randomised controlled trial.

SETTING

39 public and private hospitals across India.

PARTICIPANTS

464 adults (≥18 years) admitted to hospital (screened 22 April to 14 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO/FiO) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 235 were assigned to convalescent plasma with best standard of care (intervention arm) and 229 to best standard of care only (control arm).

INTERVENTIONS

Participants in the intervention arm received two doses of 200 mL convalescent plasma, transfused 24 hours apart. The presence and levels of neutralising antibodies were not measured a priori; stored samples were assayed at the end of the study.

MAIN OUTCOME MEASURE

Composite of progression to severe disease (PaO/FiO <100 mm Hg) or all cause mortality at 28 days post-enrolment.

RESULTS

Progression to severe disease or all cause mortality at 28 days after enrolment occurred in 44 (19%) participants in the intervention arm and 41 (18%) in the control arm (risk difference 0.008 (95% confidence interval -0.062 to 0.078); risk ratio 1.04, 95% confidence interval 0.71 to 1.54).

CONCLUSION

Convalescent plasma was not associated with a reduction in progression to severe covid-19 or all cause mortality. This trial has high generalisability and approximates convalescent plasma use in real life settings with limited laboratory capacity. A priori measurement of neutralising antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of covid-19.

TRIAL REGISTRATION

Clinical Trial Registry of India CTRI/2020/04/024775.

目的

在印度评估恢复期血浆治疗成人中度 2019 冠状病毒病（COVID-19）的疗效。

设计

开放标签、平行臂、二期、多中心、随机对照试验。

设置

印度 39 家公立和私立医院。

参与者

464 名成年人（≥18 岁）入院（筛查时间为 2020 年 4 月 22 日至 7 月 14 日），确诊为中度 COVID-19（动脉血氧分压/吸入氧分数（PaO/FiO）比值在 200mmHg 至 300mmHg 之间，或呼吸频率超过 24/min，血氧饱和度在室内空气下低于 93%）：235 名参与者接受恢复期血浆联合最佳标准治疗（干预组），229 名参与者仅接受最佳标准治疗（对照组）。

干预措施

干预组参与者接受 200mL 恢复期血浆两次输注，间隔 24 小时。预先未测量中和抗体的存在和水平；在研究结束时检测储存样本。

主要结局指标

28 天内进展为严重疾病（PaO/FiO<100mmHg）或全因死亡率的复合结局。

结果

在干预组，28 天后有 44 名（19%）参与者进展为严重疾病或全因死亡，对照组有 41 名（18%）参与者（风险差异 0.008[95%置信区间 -0.062 至 0.078]；风险比 1.04，95%置信区间 0.71 至 1.54）。

结论

恢复期血浆与 COVID-19 严重程度进展或全因死亡率降低无关。本试验具有高度普遍性，并且在实验室能力有限的情况下，近似于恢复期血浆在实际环境中的应用。在供者和参与者中预先测量中和抗体滴度可能会进一步阐明恢复期血浆在 COVID-19 管理中的作用。

试验注册

印度临床试验注册中心 CTRI/2020/04/024775。