Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: A randomized clinical trial.
Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: A randomized clinical trial.
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DOI：
10.1016/j.eclinm.2021.100773
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发表时间：
2021-03
影响因子：
15.1
通讯作者：
COVID-19 Early Treatment Study Team
中科院分区：
文献类型：
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作者：
Johnston C;Brown ER;Stewart J;Karita HCS;Kissinger PJ;Dwyer J;Hosek S;Oyedele T;Paasche-Orlow MK;Paolino K;Heller KB;Leingang H;Haugen HS;Dong TQ;Bershteyn A;Sridhar AR;Poole J;Noseworthy PA;Ackerman MJ;Morrison S;Greninger AL;Huang ML;Jerome KR;Wener MH;Wald A;Schiffer JT;Celum C;Chu HY;Barnabas RV;Baeten JM;COVID-19 Early Treatment Study Team
新冠肺炎门诊患者的治疗选择可以减少发病率，防止SARS-CoV-2传播。在这项在全美远程进行的随机、双盲、三臂(1：1：1)相当于安慰剂的对照试验中，招募了实验室确认的SARS-CoV-2感染的成年门诊患者。参与者被随机分配接受羟氯喹(HCQ)(400亿毫克，每日2次，然后是200亿毫克，每日2次，共9天)加或不加阿奇霉素(AZ)(500亿毫克，然后每天250亿毫克，共4天)或安慰剂等效物(抗坏血酸(HCQ)和叶酸(AZ))，根据进展为严重新冠肺炎的风险(高风险与低风险)进行分层。每天采集鼻拭子进行SARS-CoV-2聚合酶链式反应、流感嗜血杆菌症状调查、心电图和生命体征检查。主要终点是：(A)下呼吸道感染的14天进展、与新冠肺炎相关的28天住院或死亡；(B)14天病毒消失；次要终点包括症状消失的时间(ClinicalTrials.gov：nct04354428)。由于临床转化率低，这项研究因操作无效而终止。在2020年4月15日至7月27日期间，231名参与者参加了研究，其中219人在症状出现后开始服药，中位数为5.9天。在129名高危参与者中，6名(4.7%)发生下呼吸道感染事件(2名对照，4名HCQ/AZ)，7名(5.4%)因新冠肺炎相关住院(4名对照，1名HCQ，2名HCQ/AZ)；102名低危参与者(1名HCQ，1名HCQ/AZ)未发生LRTI，2名(2%)住院。没有人死亡。在152名登记时病毒清除的参与者中，HCQ组、HCQ/AZ组和对照组的中位清除时间分别为5天(95%CI=4-6)、6天(95%CI=4-8)和8天(95%CI=6-10)。与对照组相比，HCQ组病毒清除更快(HR=1.6 2，95%CI=1.0 1~2.6 0，P=0.0.047)，而HCQ/AZ组(HR=1.2 5，P=0.39)则无明显差异。在197名登记时符合新冠肺炎定义的参与者中，症状缓解的时间在不同组之间没有差异(HCQ：HR=1.02，95%CI-0.63-1.64，p=0.95，HCQ/AZ：HR=0.91，95%CI=0.57-1.45，p=0.70)。HCQ和HCQ/AZ均不能缩短新冠肺炎患者的临床病程，而HCQ/AZ对SARS-CoV-2病毒的脱毒只有轻微影响。HCQ和HCQ/AZ不是门诊治疗SARV-CoV-2感染的有效药物。新冠肺炎早期治疗研究由比尔和梅林达·盖茨基金会(INV-017062)通过新冠肺炎治疗加速器提供资金。华盛顿大学转化性健康科学研究所(ITHS)由NCATS/NIH资助的RedCap提供的赠款支持(UL1 TR002319)、KL2 TR002317和TL1 TR002318。内容完全由作者负责，不一定代表其所属机构的观点、决定或政策。潘和MJA得到了梅奥诊所温德兰·史密斯·赖斯综合猝死计划的支持。试验注册诊所Trials.gov编号NCT04354428
Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARS-CoV-2 transmission. In this randomized, double-blind, three-arm (1:1:1) placebo-equivalent controlled trial conducted remotely throughout the United States, adult outpatients with laboratory-confirmed SARS-CoV-2 infection were recruited. Participants were randomly assigned to receive hydroxychloroquine (HCQ) (400 mg BID x1day, followed by 200 mg BID x9days) with or without azithromycin (AZ) (500 mg, then 250 mg daily x4days) or placebo-equivalent (ascorbic acid (HCQ) and folic acid (AZ)), stratified by risk for progression to severe COVID-19 (high-risk vs. low-risk). Self-collected nasal swabs for SARS-CoV-2 PCR, FLUPro symptom surveys, EKGs and vital signs were collected daily. Primary endpoints were: (a) 14-day progression to lower respiratory tract infection (LRTI), 28-day COVID-19 related hospitalization, or death; (b) 14-day time to viral clearance; secondary endpoints included time to symptom resolution (ClinicalTrials.gov: NCT04354428). Due to the low rate of clinical outcomes, the study was terminated for operational futility. Between 15th April and 27th July 2020, 231 participants were enrolled and 219 initiated medication a median of 5.9 days after symptom onset. Among 129 high-risk participants, incident LRTI occurred in six (4.7%) participants (two control, four HCQ/AZ) and COVID-19 related hospitalization in seven (5.4%) (four control, one HCQ, two HCQ/AZ); no LRTI and two (2%) hospitalizations occurred in the 102 low-risk participants (one HCQ, one HCQ/AZ). There were no deaths. Among 152 participants with viral shedding at enrollment, median time to clearance was 5 days (95% CI=4–6) in HCQ, 6 days (95% CI=4–8) in HCQ/AZ, and 8 days (95% CI=6–10) in control. Viral clearance was faster in HCQ (HR=1.62, 95% CI=1.01–2.60, p = 0.047) but not HCQ/AZ (HR=1.25, p = 0.39) compared to control. Among 197 participants who met the COVID-19 definition at enrollment, time to symptom resolution did not differ by group (HCQ: HR=1.02, 95% CI-0.63–1.64, p = 0.95, HCQ/AZ: HR=0.91, 95% CI=0.57–1.45, p = 0.70). Neither HCQ nor HCQ/AZ shortened the clinical course of outpatients with COVID-19, and HCQ, but not HCQ/AZ, had only a modest effect on SARS-CoV-2 viral shedding. HCQ and HCQ/AZ are not effective therapies for outpatient treatment of SARV-CoV-2 infection. The COVID-19 Early Treatment Study was funded by the Bill & Melinda Gates Foundation (INV-017062) through the COVID-19 Therapeutics Accelerator. University of Washington Institute of Translational Health Science (ITHS) grant support (UL1 TR002319), KL2 TR002317, and TL1 TR002318 from NCATS/NIH funded REDCap. The content is solely the responsibility of the authors and does not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. PAN and MJA were supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. Trial registration ClinicalTrials.gov number NCT04354428
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影响因子：
9.4
作者：
Lieberman, Joshua A.;Pepper, Gregory;Greninger, Alexander L.
通讯作者：
Greninger, Alexander L.
影响因子：
39.2
作者：
Skipper, Caleb P.;Pastick, Katelyn A.;Boulware, David R.
通讯作者：
Boulware, David R.
DOI：
10.1007/s10096-020-03913-9
发表时间：
2020-04-27
影响因子：
4.5
作者：
La Scola, Bernard;Le Bideau, Marion;Raoult, Didier
通讯作者：
Raoult, Didier
DOI：
10.1016/j.ijantimicag.2020.105949
发表时间：
2020-07-01
影响因子：
10.8
作者：
Gautret, Philippe;Lagier, Jean-Christophe;Raoult, Didier
通讯作者：
Raoult, Didier
DOI：
10.15585/mmwr.mm6912e2
发表时间：
2020-03-27
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
CDC COVID-19 Response Team
通讯作者：
CDC COVID-19 Response Team