Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 A Randomized Trial
Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 A Randomized Trial
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DOI：
10.7326/m20-4207
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发表时间：
2020-10-20
影响因子：
39.2
通讯作者：
Boulware, David R.
中科院分区：
文献类型：
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作者：
Skipper, Caleb P.;Pastick, Katelyn A.;Boulware, David R.
背景：目前尚无有效的口服疗法治疗2019年早期冠状病毒病(新冠肺炎)。目的：探讨羟基氯喹是否可以减轻成人门诊患者新冠肺炎的严重程度。设计：2020年3月22日至5月20日进行的随机、双盲、安慰剂对照试验。(临床试验.gov：NCT04308668)地点：美国和加拿大(40个州和3个省)的基于互联网的试验。参与者：有症状的非住院成年人，经实验室确认患有新冠肺炎或可能患有新冠肺炎，并在症状出现后4天内有高风险暴露。干预：口服羟氯喹(一次800毫克，然后在6到8小时内600毫克，然后每天600毫克，持续4天以上)或遮盖式安慰剂。测量：基线，然后在第3、5、10和14天使用10分视觉模拟评分的症状和严重程度。主要终点是总症状严重程度在14天内的变化。结果：在随机分配到一组的491名患者中，423人提供了主要终点数据。在这些人中，341人(81%)经实验室确认感染了严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)，或与实验室确认感染的人有流行病学联系；56%(423人中的236人)在出现症状后1天内登记。14天后症状严重程度的变化在羟氯喹组和安慰剂组之间没有差异(症状严重程度的差异：相对的，12%；绝对的，-0.27点[95%CI，-0.61点到0.07点]；P=0.117)。14天后，接受羟氯喹治疗的参与者中有24%(49人)出现持续症状，相比之下，接受安慰剂治疗的参与者中有30%(59人)出现持续症状(P=0.21)。服用羟氯喹的参与者中，43%(92/212)发生了药物不良反应，而服用安慰剂的受试者中，有22%(46/211)发生了药物不良反应(P<；0.001)。在服用安慰剂的情况下，发生了10次住院治疗(2次与新冠肺炎无关)，包括1次住院死亡。使用羟氯喹，有4次住院和1次非住院死亡(P=0.29)。限制：由于美国严重的检测缺陷，只有58%的参与者接受了SARS-CoV-2检测。结论：羟基氯喹没有显著降低早期轻度COVID-19门诊患者的症状严重程度。主要资金来源：私人捐赠者。
Background: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).Objective: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.Design: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials .gov: NCT04308668)Setting: Internet-based trial across the United States and Canada (40 states and 3 provinces).Participants: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.Intervention: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo.Measurements: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.Results: Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P =0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19 -related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).Limitation: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.Conclusion: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.Primary Funding Source: Private donors.