Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial.
Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial.
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DOI：
10.1001/jamainternmed.2020.6319
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发表时间：
2021-02-01
影响因子：
39
通讯作者：
Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) Investigators
中科院分区：
文献类型：
--
作者：
Abella BS;Jolkovsky EL;Biney BT;Uspal JE;Hyman MC;Frank I;Hensley SE;Gill S;Vogl DT;Maillard I;Babushok DV;Huang AC;Nasta SD;Walsh JC;Wiletyo EP;Gimotty PA;Milone MC;Amaravadi RK;Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) Investigators
当医院卫生保健工作者采用每日600毫克羟氯喹方案作为暴露前预防策略时，是否可以减少严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的传播？在这项包括132名参与者的双盲、安慰剂对照随机临床试验中，羟氯喹组和安慰剂组在逆转录酶聚合酶链反应证实的SARS-CoV-2发病率方面没有显著差异。在医院医务人员中，每日服用羟氯喹并不能预防SARS-CoV-2感染，尽管该试验被提前终止，可能不足以发现临床上重要的差异。护理2019冠状病毒病（COVID-19）患者的卫生保健工作者有暴露于严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的风险。目前，据我们所知，对高危人群没有有效的药物预防。采用暴露前预防策略，评价羟氯喹在接触COVID-19患者的医院卫生保健人员中预防SARS-CoV-2传播的效果。这项随机、双盲、安慰剂对照的临床试验（羟氯喹预防和治疗COVID-19研究）在2个三级城市医院进行，入组时间为2020年4月9日至2020年7月14日；后续工作于2020年8月4日结束。该试验随机选取了132名全职医院医护人员（医生、护士、持证护理助理、急救技术人员和呼吸治疗师），其中125人最初无症状，鼻咽拭子检测结果为SARS-CoV-2阴性。在计划招募200名参与者之前，该试验因无效而提前终止。羟氯喹，600毫克，每日，或口服大小匹配的安慰剂，连续8周。主要终点是8周治疗期间通过鼻咽拭子测定的SARS-CoV-2感染发生率。次要结局包括不良反应、停止治疗、SARS-CoV-2抗体的存在、QTc延长的频率和SARS-CoV-2阳性参与者的临床结局。在132名随机受试者中（中位年龄33岁[范围，20-66岁]；91名女性[69%]），125名（94.7%）可评估主要结局。与安慰剂相比，随机接受羟氯喹治疗的参与者的感染率没有显著差异（64人中有4人[6.3%]vs 61人中有4人[6.6%];P < 0.05）。轻度不良事件在服用羟氯喹的参与者中比安慰剂更常见（45% vs 26%; P = 0.04）；两组的停药率相似（19% vs 16%; P = 0.81）。两组间QTc的中位变化（基线至4周评估）无差异（羟氯喹：4毫秒；95% CI， - 9至17；安慰剂：3毫秒；95% CI， - 5至11；P = 0.98）。在8名SARS-CoV-2阳性结果的参与者中（6.4%），6人出现病毒症状；没有人需要住院治疗，所有人临床康复。在这项随机临床试验中，尽管受到早期终止的限制，但在暴露于COVID-19患者的医院卫生保健人员中，每天给予羟氯喹8周作为暴露前预防没有临床益处。这项随机临床试验评估了在宾夕法尼亚州费城的两家医院中，羟氯喹在与COVID-19患者接触的医护人员中预防SARS-CoV-2传播的有效性。
Does a regimen of hydroxychloroquine, 600 mg, per day, reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pre-exposure prophylaxis strategy when taken by hospital-based health care workers? In this double-blind, placebo-controlled randomized clinical trial that included 132 participants and was terminated early, there was not a significant difference in reverse-transcriptase polymerase chain reaction–confirmed SARS-CoV-2 incidence between hydroxychloroquine and placebo cohorts. Among hospital-based health care workers, daily hydroxychloroquine did not prevent SARS-CoV-2 infection, although the trial was terminated early and may have been underpowered to detect a clinically important difference. Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants. Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks. The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2–positive participants. Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, −9 to 17; vs placebo: 3 milliseconds; 95% CI, −5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered. In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19. ClinicalTrials.gov Identifier: NCT04329923 This randomized clinical trial evaluates the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in health care workers with exposure to patients with COVID-19 at 2 hospitals in Philadelphia, Pennsylvania.
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影响因子：
11.8
作者：
Tai, Don Bambino Geno;Shah, Aditya;Wieland, Mark L.
通讯作者：
Wieland, Mark L.
DOI：
10.1056/nejmoa2022926
发表时间：
2020-11-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
RECOVERY Collaborative Group;Horby P;Mafham M;Linsell L;Bell JL;Staplin N;Emberson JR;Wiselka M;Ustianowski A;Elmahi E;Prudon B;Whitehouse T;Felton T;Williams J;Faccenda J;Underwood J;Baillie JK;Chappell LC;Faust SN;Jaki T;Jeffery K;Lim WS;Montgomery A;Rowan K;Tarning J;Watson JA;White NJ;Juszczak E;Haynes R;Landray MJ
通讯作者：
Landray MJ
影响因子：
158.5
作者：
Boulware, David R.;Pullen, Matthew F.;Hullsiek, Kathy H.
通讯作者：
Hullsiek, Kathy H.
影响因子：
12.7
作者：
Ye, Chanyuan;Zhang, Shanyan;Yang, Yida
通讯作者：
Yang, Yida
影响因子：
24
作者：
Puntmann, Valentina O.;Carerj, M. Ludovica;Nagel, Eike
通讯作者：
Nagel, Eike