Barcelona Institute for Global Health (ISGlobal), Hospital Clínic - University of Barcelona, Rosselló 132 4rt 1a, 08036, Barcelona, Spain.
Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
Trials. 2021 Nov 15;22(1):808. doi: 10.1186/s13063-021-05758-9.
Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period.
We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets.
52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041).
Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe.
ClinicalTrials.gov NCT04331834 . Registered on April 2, 2020.
暴露前预防（PrEP）是打破 COVID-19 传播的有希望的策略。尽管羟氯喹已被评估用于治疗和暴露后预防，但尚未评估其在 COVID-19 PrEP 中的作用。本研究的目的是评估在流行期间，高风险 SARS-CoV-2 感染的医护人员中使用羟氯喹进行 PrEP 的疗效和安全性。
我们在西班牙巴塞罗那的三家医院进行了一项双盲安慰剂对照随机临床试验。在 350 名筛查的成年医护人员中，我们纳入了 269 名无活动性或既往 SARS-CoV-2 感染的参与者（通过鼻咽 SARS-CoV-2 PCR 阴性和 SARS-CoV-2 血清学阴性确定）。分配到干预组（PrEP）的参与者在前四天每天接受 400mg 羟氯喹，随后在研究期间每周接受 400mg。对照组参与者遵循相同的治疗方案，使用安慰剂片。
269 名参与者中，52.8%（142/269）在羟氯喹组，47.2%（127/269）在安慰剂组。鉴于全国疫情发病率下降，两组各有一名参与者被诊断出 COVID-19。由于无效，试验停止，我们的研究设计被认为不足以评估 PrEP 疗效的任何益处。两组均有相似比例的参与者发生至少一次不良事件（AE）（p=0.548）。未报告严重 AE。几乎所有 AE（96.4%，106/110）均为轻度。与安慰剂组相比，羟氯喹组仅轻度胃肠道症状显著更高（27.4%（39/142）vs 15.7%（20/127），p=0.041）。
尽管无法评估羟氯喹预防 COVID-19 的 PrEP 效果，但我们的研究表明，低剂量羟氯喹的 PrEP 是安全的。
ClinicalTrials.gov NCT04331834。注册于 2020 年 4 月 2 日。
