Department of Internal Medicine, Medical School and Telehealth Center, University Hospital, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena 190, sala 246, Belo Horizonte, 30130-100, Brazil.
Institute for Health Technology Assessment (IATS/CNPq), Rua Ramiro Barcelos, 2359, Prédio 21|Sala 507, Porto Alegre, Brazil.
BMC Infect Dis. 2022 Jul 23;22(1):639. doi: 10.1186/s12879-022-07589-8.
The role of ivermectin in the treatment of COVID-19 is still under debate, yet the drug has been widely used in some parts of the world, as shown by impressive market data. The available body of evidence may have changed over the last months, as studies have been retracted and "standards of care" (SOC) used in control groups have changed with rapidly evolving knowledge on COVID-19. This review aims to summarize and critically appraise the evidence of randomized controlled trials (RCTs) of ivermectin, assessing clinical outcomes in COVID-19 patients.
RCTs evaluating the effects of ivermectin in adult patients with COVID-19 were searched through June 22, 2022, in four databases, L.OVE platform, clinical trial registries and pre-prints platforms. Primary endpoints included all-cause mortality and invasive ventilation requirement. Secondary endpoint was the occurrence of adverse events. Risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Meta-analysis included only studies which compared ivermectin to placebo or SOC. Random-effects were used to pool the risk ratios (RRs) of individual trials. The quality of evidence was evaluated using GRADE. The protocol was register in PROSPERO (CRD42021257471).
Twenty-five RCTs fulfilled inclusion criteria (n = 6310). Of those, 14 compared ivermectin with placebo, in night ivermectin associated with SOC was compared to SOC and two studies compared ivermectin to an active comparator. Most RCTs had some concerns or high risk of bias, mostly due to lack of concealment of the randomization sequence and allocation, lack of blinding and high number of missing cases. Ivermectin did not show an effect in reducing mortality (RR = 0.76; 95%CI: 0.52-1.11) or mechanical ventilation (RR = 0.74; 95%CI: 0.48-1.16). This effect was consistent when comparing ivermectin vs. placebo, and ivermectin associated with SOC vs. SOC, as well as in sensitivity analysis. Additionally, there was very low quality of evidence regarding adverse effects (RR = 1.07; 95%CI: 0.84-1.35).
The evidence suggests that ivermectin does not reduce mortality risk and the risk of mechanical ventilation requirement. Although we did not observe an increase in the risk of adverse effects, the evidence is very uncertain regarding this endpoint.
伊维菌素在 COVID-19 治疗中的作用仍存在争议，但该药物在世界某些地区已被广泛使用，这从令人印象深刻的市场数据中可见一斑。随着对 COVID-19 的认识不断发展，可用的证据体可能在过去几个月发生了变化，因为研究被撤回，对照组中使用的“标准治疗”（SOC）也发生了变化。本综述旨在总结和批判性评估伊维菌素随机对照试验（RCT）的证据，评估 COVID-19 患者的临床结局。
通过 2022 年 6 月 22 日在四个数据库、L.OVE 平台、临床试验注册处和预印本平台中检索评估伊维菌素对成年 COVID-19 患者影响的 RCT。主要终点包括全因死亡率和有创通气需求。次要终点是不良事件的发生。使用 Cochrane 风险偏倚 2.0 工具评估风险偏倚。仅对比较伊维菌素与安慰剂或 SOC 的研究进行荟萃分析。使用随机效应汇总个体试验的风险比（RR）。使用 GRADE 评估证据质量。方案在 PROSPERO（CRD42021257471）中注册。
25 项 RCT 符合纳入标准（n=6310）。其中，14 项比较了伊维菌素与安慰剂，伊维菌素联合 SOC 与 SOC 进行比较，两项研究比较了伊维菌素与活性对照药物。大多数 RCT 存在一些关注或高风险的偏倚，主要是由于随机序列和分配的隐藏、盲法和大量缺失病例缺乏。伊维菌素在降低死亡率（RR=0.76；95%CI：0.52-1.11）或机械通气（RR=0.74；95%CI：0.48-1.16）方面没有显示出效果。这种效果在比较伊维菌素与安慰剂以及伊维菌素与 SOC 联合 SOC 时是一致的，在敏感性分析中也是一致的。此外，关于不良反应的证据质量非常低（RR=1.07；95%CI：0.84-1.35）。
证据表明，伊维菌素不能降低死亡率风险和机械通气需求的风险。虽然我们没有观察到不良反应风险增加，但关于这一终点的证据非常不确定。
