Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19 A Randomized Clinical Trial
Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19 A Randomized Clinical Trial
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DOI：
10.1001/jama.2020.22240
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发表时间：
2020-11-09
影响因子：
120.7
通讯作者：
Brown, Samuel M.
中科院分区：
文献类型：
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作者：
Self, Wesley H.;Semler, Matthew W.;Brown, Samuel M.
重要性需要有关羟氯喹治疗2019冠状病毒病（COVID-19）的疗效数据。目的确定羟氯喹是否是治疗因COVID-19住院的成人的有效方法。设计、设置和参与者这是一项在美国34家医院进行的多中心、盲法、安慰剂对照随机试验。2020年4月2日至6月19日期间因严重急性呼吸综合征冠状病毒2型感染的呼吸道症状住院的成人入组，末次结局评估日期为2020年7月17日。计划的样本量为510例患者，计划在每102例患者入组后进行中期分析。试验在第四次中期分析时因无效而停止，样本量为479例患者。干预患者被随机分配到羟氯喹（400毫克，每日两次，2剂，然后200毫克，每日两次，8剂）（n = 242）或安慰剂（n = 237）。主要结果和测量主要结果是随机分组后14天的临床状态，用7类顺序量表进行评估，范围从1（死亡）到7（出院并能够进行正常活动）。采用多变量比例优势模型分析主要结局，校正优势比（aOR）大于1.0表明羟氯喹的结局优于安慰剂。该试验包括12个次要结局，包括28天死亡率。结果479例患者随机分为两组，（中位年龄57岁; 44.3%女性; 37.2%西班牙裔/拉丁裔; 23.4%黑人; 20.1%在重症监护室; 46.8%接受无正压辅助供氧; 11.5%接受无创通气或鼻高流量氧; 6.7%接受有创机械通气或体外膜肺氧合），433例（90.4%）在14天时完成了主要结局评估，其余患者进行了临床状态插补。随机化前症状的中位持续时间为5天（四分位距[IQR]，3 - 7天）。第14天，羟氯喹组和安慰剂组的顺序结局量表的临床状态无显著差异（中位数[IQR]评分，6 [4-7] vs 6 [4-7]; aOR，1.02 [95% CI，0.73 - 1.42]）。两组之间的12个次要结局均无显著差异。随机分组后28天，羟氯喹组241例患者中有25例（10.4%）死亡，安慰剂组236例患者中有25例（10.6%）死亡（绝对差异，-0.2% [95% CI，-5.7%至5.3%]; aOR，1.07 [95% CI，0.54至2.09]）。结论和相关性在因COVID-19呼吸系统疾病住院的成年人中，与安慰剂相比，羟氯喹治疗在第14天没有显著改善临床状态。这些发现并不支持在住院成人中使用羟氯喹治疗COVID-19。
Importance Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.