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Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial.
BMJ. 2020 05 14; 369:m1849.BMJ

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.

TRIAL REGISTRATION

ChiCTR2000029868.

Authors+Show Affiliations

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.Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.Department of Respiratory Medicine, No 2 People's Hospital of Fuyang City, Fuyang, Anhui, China.Department of Respiratory Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, China.Department of Respiratory and Critical Care Medicine, Xiangyang No 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.Department of Infectious Diseases, Central Hospital of Ezhou, Ezhou, Hubei, China.Department of Cardiovascular Medicine, Yunmeng People's Hospital, Xiaogan, Hubei, China.Department of Respiratory Medicine, First People's Hospital of Jingzhou City, Jingzhou, Hubei, China.Department of Infectious Diseases, Xiaogan Hospital Affiliated to Wuhan University of Science and Technology, Xiaogan, Hubei, China.Department of Emergency Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.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.Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.Department of Respiratory Medicine, Hubei Space Hospital of Xiaogan, Xiaogan, Hubei, China.Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.Department of Infectious Disease, The Sixth People's Hospital of Zhengzhou, Zhengzhou, Henan, China.Department of Infectious Disease, Wuhan No 7 Hospital, Wuhan, Hubei, China.Departments of Respiratory Medicine, Xiaogan Hospital Affiliated to Wuhan University of Science and Technology, Xiaogan, Hubei, China xieqingrjh@163.com.Department of Respiratory Medicine, The Third People's Hospital of Yichang, Yichang, Hubei, China.Department of Respiratory Medicine, Xiao Gan First People's Hospital, Xiaogan, Hubei Province, China.Clinical Research Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.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.Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.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.Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China xieqingrjh@163.com.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32409561

Citation

Tang, Wei, et al. "Hydroxychloroquine in Patients With Mainly Mild to Moderate Coronavirus Disease 2019: Open Label, Randomised Controlled Trial." BMJ (Clinical Research Ed.), vol. 369, 2020, pp. m1849.
Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849.
Tang, W., Cao, Z., Han, M., Wang, Z., Chen, J., Sun, W., Wu, Y., Xiao, W., Liu, S., Chen, E., Chen, W., Wang, X., Yang, J., Lin, J., Zhao, Q., Yan, Y., Xie, Z., Li, D., Yang, Y., ... Xie, Q. (2020). Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ (Clinical Research Ed.), 369, m1849. https://doi.org/10.1136/bmj.m1849
Tang W, et al. Hydroxychloroquine in Patients With Mainly Mild to Moderate Coronavirus Disease 2019: Open Label, Randomised Controlled Trial. BMJ. 2020 05 14;369:m1849. PubMed PMID: 32409561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. AU - Tang,Wei, AU - Cao,Zhujun, AU - Han,Mingfeng, AU - Wang,Zhengyan, AU - Chen,Junwen, AU - Sun,Wenjin, AU - Wu,Yaojie, AU - Xiao,Wei, AU - Liu,Shengyong, AU - Chen,Erzhen, AU - Chen,Wei, AU - Wang,Xiongbiao, AU - Yang,Jiuyong, AU - Lin,Jun, AU - Zhao,Qingxia, AU - Yan,Youqin, AU - Xie,Zhibin, AU - Li,Dan, AU - Yang,Yaofeng, AU - Liu,Leshan, AU - Qu,Jieming, AU - Ning,Guang, AU - Shi,Guochao, AU - Xie,Qing, Y1 - 2020/05/14/ PY - 2020/5/16/entrez PY - 2020/5/16/pubmed PY - 2020/5/20/medline SP - m1849 EP - m1849 JF - BMJ (Clinical research ed.) JO - BMJ VL - 369 N2 - 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. TRIAL REGISTRATION: ChiCTR2000029868. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/32409561/full_citation L2 - http://www.bmj.com/cgi/pmidlookup?view=long&pmid=32409561 DB - PRIME DP - Unbound Medicine ER -