Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial
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
BMJ, doi:10.1136/bmj.m1849
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 nonrecipients 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.
TRIAL REGISTRATION ChiCTR2000029868.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work other than those listed above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: The trial was approved by the Institutional Review Board of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (KY2020-29). All patients gave written informed consent. Data sharing: Anonymised datasets can be made available on reasonable request after approval from the trial management committee and after signing of a data access agreement. Proposals should be directed to the corresponding author. The lead authors (the manuscript's guarantors) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Dissemination to participants and related patient and public communities: There are no plans to disseminate the results of the research to study participants or the relevant patient community.
Web appendix: Supplement Web appendix: Supplementary tables on 16 January 2022 by guest. Protected by copyright...
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'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Multicentre, '
'open label, randomised controlled '
'trial.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>16 government '
'designated covid-19 treatment centres in China, 11 to 29 February '
'2020.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec><jats:title>Main '
'outcome measure</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of 150 patients, '
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'events.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Administration '
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