羟氯喹啉与安慰剂治疗非住院COVID-19患者的疗效比较（COPE - 联盟V）：一项双盲、多中心、随机对照试验。
Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE - Coalition V): A double-blind, multicentre, randomised, controlled trial.
作者信息
Avezum Álvaro, Oliveira Gustavo B F, Oliveira Haliton, Lucchetta Rosa C, Pereira Valéria F A, Dabarian André L, D O Vieira Ricardo, Silva Daniel V, Kormann Adrian P M, Tognon Alexandre P, De Gasperi Ricardo, Hernandes Mauro E, Feitosa Audes D M, Piscopo Agnaldo, Souza André S, Miguel Carlos H, Nogueira Vinicius O, Minelli César, Magalhães Carlos C, Morejon Karen M L, Bicudo Letícia S, Souza Germano E C, Gomes Marco A M, Fo José J F Raposo, Schwarzbold Alexandre V, Zilli Alexandre, Amazonas Roberto B, Moreira Frederico R, Alves Lucas B O, Assis Silvia R L, Neves Precil D M M, Matuoka Jessica Y, Boszczowski Icaro, Catarino Daniela G M, Veiga Viviane C, Azevedo Luciano C P, Rosa Regis G, Lopes Renato D, Cavalcanti Alexandre B, Berwanger Otavio
机构信息
International Research Center, Hospital Alemão Oswaldo Cruz, Rua Treze de Maio, 1815; Bloco A, 1o SS, São Paulo, SP 01327-001, Brazil.
ALPHACOR Cardiologia Clínica e Diagnóstica, Barueri, SP, Brazil.
出版信息
Lancet Reg Health Am. 2022 Jul;11:100243. doi: 10.1016/j.lana.2022.100243. Epub 2022 Mar 31.
BACKGROUND
Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers.
METHODS
We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540.
FINDINGS
From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04]).
INTERPRETATION
In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting.
FUNDING
COALITION COVID-19 Brazil and EMS.
背景
既往评估氯喹和羟氯喹在非住院COVID-19患者中疗效的随机对照试验（RCT）发现，住院率无显著差异。然而，统计效能较低，无法得出明确结论。
方法
我们在巴西的56个地点进行了一项多中心、双盲RCT。纳入发病≤7天、有疑似或确诊COVID-19且症状为轻至中度、至少有一项临床恶化风险因素的成人患者，按1:1随机分组，分别接受羟氯喹治疗（第1天400mg每日2次，之后400mg每日1次，共7天）或匹配的安慰剂。主要结局为30天时因COVID-19住院，由对治疗分配不知情的裁决委员会按照意向性分析（ITT）原则进行评估。仅对经分子或血清学检测确诊为SARS-CoV-2感染的参与者进行了额外分析（改良ITT [mITT]分析）。本试验已在ClinicalTrials.gov注册，注册号为NCT04466540。
结果
2020年5月12日至2021年7月7日，1372例患者被随机分配至羟氯喹组或安慰剂组。羟氯喹组和安慰剂组的住院风险无显著差异（分别为44/689 [6.4%]和57/683 [8.3%]，RR 0.77 [95% CI 0.52 - 1.12]，p = 0.16）；mITT分析结果相似，事件发生率分别为43/478 [9.0%]和55/471 [11.7%]，RR 0.77 [95% CI 0.53 - 1.12]，p = 0.17。为进一步补充数据，我们进行了一项荟萃分析，结果表明羟氯喹在降低检测阳性患者的住院率方面无显著益处（分别为69/1222 [5.6%]和88/1186 [7.4%]；RR 0.77 [95% CI 0.57 - 1.04]）。
解读
在轻度或中度COVID-19门诊患者中，与安慰剂对照相比，使用羟氯喹并未降低住院风险。我们的研究结果不支持在门诊环境中常规使用羟氯喹治疗COVID-19。
资助
巴西COVID-19联盟和EMS。
Zotero 插件