上海交通大学医学院谢青团队近期取得新进展。他们探讨了羟氯喹治疗covid-19轻中症患者的疗效和安全性。该成果于2020年5月14日发表在《英国医学杂志》上。

为了评估羟氯喹联合标准治疗与单独标准治疗相比，在成人covid-19中的疗效和安全性，2020年2月11日至29日，研究组在我国16个政府指定的covid-19治疗中心进行了一项多中心、开放标签、随机对照试验。招募了150例经实验室确诊的covid-19入院患者，将其按1：1随机分组，其中75例接受羟氯喹+标准治疗，75例仅接受标准治疗。150例患者中148例为轻中症，2例为重症。从症状发作到随机分组的平均持续时间为16.6天。

共有109（73％）名患者（标准治疗组56名，羟氯喹+标准治疗组53名）在28天内新冠病毒转阴，其余41例（27％）患者由于病毒未转阴，对其进行检查。羟氯喹+标准治疗组在28天内出现转阴的可能性为85.4％，标准治疗组为81.3％，组间差异为4.1％，无统计学意义。在安全人群中，羟氯喹接受者中有30%发生不良事件，未接受羟氯喹者中有9%。羟氯喹接受者中最常见的不良事件是腹泻，发生率为10％。两名羟氯喹接受者发生严重不良事件。

总之，在轻中症covid-19持续住院的患者中，接受羟氯喹治疗与仅标准治疗相比，并未提高病毒转阴率，且不良事件发生率较高。

附：英文原文

Title: Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

Author: Wei Tang, Zhujun Cao, Mingfeng Han, Zhengyan Wang, Junwen Chen, Wenjin Sun, Yaojie Wu, Wei Xiao, Shengyong Liu, Erzhen Chen, Wei Chen, Xiongbiao Wang, Jiuyong Yang, Jun Lin, Qingxia Zhao, Youqin Yan, Zhibin Xie, Dan Li, Yaofeng Yang, Leshan Liu, Jieming Qu, Guang Ning, Guochao Shi, Qing Xie

Issue&Volume: 2020/05/14

Abstract: Objective To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19).

Design Multicentre, open label, randomised controlled trial.

Setting 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020.

Participants 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone).

Interventions Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively).

Main outcome measure Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone.

Results Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval –10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events.

Conclusions Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients.

DOI: 10.1136/bmj.m1849

Source: https://www.bmj.com/content/369/bmj.m1849