Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
BMJ. 2020 May 14;369:m1849. doi: 10.1136/bmj.m1849.
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).
Multicentre, open label, randomised controlled trial.
16 government designated covid-19 treatment centres in China, 11 to 29 February 2020.
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).
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).
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.
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.
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.
ChiCTR2000029868.
评估羟氯喹联合标准治疗与单纯标准治疗相比，在成人 2019 冠状病毒病（covid-19）患者中的疗效和安全性。
多中心、开放标签、随机对照试验。
中国 16 家政府指定的 covid-19 治疗中心，2020 年 2 月 11 日至 29 日。
150 名因实验室确诊的 covid-19 而入院的患者被纳入意向治疗分析（75 名患者被分配接受羟氯喹联合标准治疗，75 名患者接受标准治疗）。
羟氯喹的负荷剂量为每日 1200mg，连用 3 天，随后维持剂量为每日 800mg（轻度至中度疾病患者的总治疗时间分别为 2 或 3 周，严重疾病患者为 4 周）。
28 天内严重急性呼吸综合征冠状病毒 2 的阴性转换，根据意向治疗原则进行分析。在安全性人群中分析不良事件，其中羟氯喹组的接受者为至少接受过一次羟氯喹治疗的参与者，而羟氯喹非接受者为仅接受标准治疗的参与者。
在 150 名患者中，148 名患者为轻度至中度疾病，2 名患者为严重疾病。从症状出现到随机分组的平均时间为 16.6（标准差 10.5；范围 3-41）天。共有 109 名（73%）患者（56 名标准治疗；53 名标准治疗加羟氯喹）在 28 天前出现了病毒的阴性转换，其余 41 名（27%）患者（19 名标准治疗；22 名标准治疗加羟氯喹）因未达到病毒阴性转换而被删失。标准治疗加羟氯喹组在 28 天内出现阴性转换的概率为 85.4%（95%置信区间 73.8%至 93.8%），与标准治疗组相似（81.3%，71.2%至 89.6%）。两组之间的差异为 4.1%（95%置信区间-10.3%至 18.5%）。在安全性人群中，7/80（9%）名羟氯喹非接受者和 21/70（30%）名羟氯喹接受者记录了不良事件。羟氯喹接受者中最常见的不良事件是腹泻，7/70（10%）名患者出现这种情况。有 2 名羟氯喹接受者报告了严重不良事件。
与单纯标准治疗相比，羟氯喹治疗并不能显著提高入院时主要为持续性轻度至中度 covid-19 患者的病毒阴性转换率。羟氯喹组的不良事件发生率高于非羟氯喹组。
ChiCTR2000029868。
