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J Zhejiang Univ (Med Sci)  2020, Vol. 49 Issue (2): 215-219    DOI: 10.3785/j.issn.1008-9292.2020.03.03
    
A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19
CHEN Jun(),LIU Danping,LIU Li,LIU Ping,XU Qingnian,XIA Lu,LING Yun,HUANG Dan,SONG Shuli,ZHANG Dandan,QIAN Zhiping,LI Tao,SHEN Yinzhong,LU Hongzhou*()
Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
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Abstract  

Objective: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19). Methods: We prospectively enrolled 30 treatment-naïve patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1:1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517). Results: One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1, 9) days in HCQ group, which is comparable to that in the control group [2 (1, 4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0, 2) day after hospitalization, which was also comparable to that in the control group [1 (0, 3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05). Conclusions: The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.



Key wordsCoronavirus disease 2019      Severe acute respiratory syndrome coronavirus 2      Novel coronavirus pneumonia      Hydroxychloroquine      Treatment outcome      Safety      Randomized controlled trial     
Received: 29 February 2020      Published: 06 March 2020
CLC:  R512.99  
Corresponding Authors: LU Hongzhou     E-mail: qtchenjun@163.com;luhongzhou@fudan.edu.cn
Cite this article:

CHEN Jun,LIU Danping,LIU Li,LIU Ping,XU Qingnian,XIA Lu,LING Yun,HUANG Dan,SONG Shuli,ZHANG Dandan,QIAN Zhiping,LI Tao,SHEN Yinzhong,LU Hongzhou. A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19. J Zhejiang Univ (Med Sci), 2020, 49(2): 215-219.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.03.03     OR     http://www.zjujournals.com/med/Y2020/V49/I2/215


硫酸羟氯喹治疗2019冠状病毒病(COVID-19)普通型患者的初步研究

目的: 初步评价硫酸羟氯喹治疗2019冠状病毒病(COVID-19)普通型患者的疗效和安全性。方法: 收集2020年2月6至25日在上海市公共卫生临床中心住院治疗的30例COVID-19普通型患者。患者1:1随机分配到试验组和对照组。对照组接受常规治疗,试验组在常规治疗的基础上口服硫酸羟氯喹(400 mg,1次/d)治疗,疗程为5 d。比较两组治疗第7天时咽拭子病毒核酸转阴率等指标。研究获上海市公共卫生临床中心伦理委员会批准,并登记注册(NCT04261517)。结果: 在治疗过程中,试验组1例患者发展为重型。入组后第7天,试验组中13例(86.7%)和对照组中14例(93.3%)患者咽拭子病毒核酸检测为阴性(P>0.05)。在2周的访视期内,所有受试者的咽拭子核酸检测均转为阴性,其中试验组咽拭子核酸转阴时间为入院后第4(1,9)天,对照组为第2(1,4)天,差异无统计学意义(Z=1.27,P>0.05)。试验组在入院后第1(0,2)天体温恢复正常,对照组在入院后第1(0,3)天体温恢复正常。影像学检查结果显示,试验组5例(33.3%)和对照组7例(46.7%)患者均在入院3 d后的复查中出现了进展,所有患者在随后的复查中均提示病灶好转。试验组和对照组分别有4例(26.7%)和3例(20.0%)患者出现一过性的腹泻和肝功能异常等不良反应,两组不良反应发生率差异无统计学意义(P>0.05)。结论: 目前COVID-19普通型患者预后较好,以病毒转阴率、重症化率为主要终点的研究难以对药物的疗效进行判断。开展后续的研究需要确定更合适的人群和终点事件,并充分考虑样本量等试验的可行性问题。


关键词: 2019冠状病毒病,  严重急性呼吸综合征冠状病毒2,  新型冠状病毒肺炎,  羟氯喹,  治疗结果,  安全性,  随机对照试验 
组别 n 男性* 平均年龄
(岁)
平均病程(d) 发热 基础疾病* 白细胞计数(×109/L) 淋巴细胞计数
(×109/L)
ALT
(U/L)
eGFR
(mL·min-1·1.73m-2)
乳酸
(mmol/L)
CD4+细胞
计数(/μL)
胸部CT病灶
(两肺/一侧肺)*
高血压 糖尿病 慢性阻塞性肺疾病
  “—”无相关数据.*Fisher检验.ALT:丙氨酸转氨酶;eGFR:肾小球滤过率估值.
试验组 15 9(60.0) 50.5±3.8 6.6±3.9 9(60.0) 5(33.3) 1(6.7) 0(0.0) 5.2(3.9,6.7) 1.11±0.43 18(15,23) 117±29 1.4±0.4 415(275,589) 12/3
对照组 15 12(80.0) 46.7±3.6 5.9±4.1 13(86.7) 3(20.0) 1(6.7) 1(6.7) 4.9(4.5,7.4) 1.18±0.55 24(14,47) 120±29 1.4±0.5 395(272,710) 14/1
t/U 0.72 0.45 101 0.39 87 0.30 0.19 110
P >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Tab 1 Demographic data and clinical characteristics of the two groups  [$\bar x \pm s$或M(Q1, Q3)或n(%)]
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