Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Universidad Científica del Sur, Lima, Peru.
Clin Infect Dis. 2022 Mar 23;74(6):1022-1029. doi: 10.1093/cid/ciab591.
We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease 2019 (COVID-19).
Published and preprint randomized controlled trials (RCTs) assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March 2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay (LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs (SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods.
Ten RCTs (n = 1173) were included. The controls were the standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates compared with controls (relative risk [RR], 0.37 [95% confidence interval, .12-1.13]; very low QoE) or LOS compared with controls (mean difference, 0.72 days [95% confidence interval, -.86 to 2.29 days]; very low QoE). AEs, SAEs, and viral clearance were similar between IVM and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were reduced with IVM.
Compared with the standard of care or placebo, IVM did not reduce all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with COVID-19.
我们系统评估了伊维菌素(IVM)在 COVID-19 患者中的使用的获益和危害。
我们在 5 个引擎中检索了截至 2021 年 3 月 22 日评估 IVM 对 COVID-19 成年患者影响的已发表和预印本随机对照试验(RCT)。主要结局为全因死亡率、住院时间(LOS)和不良事件(AE)。次要结局包括病毒清除率和严重不良事件(SAE)。使用 Cochrane 风险偏倚 2.0 工具评估风险偏倚(RoB)。采用逆方差随机效应荟萃分析,使用 GRADE 方法评估证据质量(QoE)。
纳入了 10 项 RCT(n=1173)。对照组在 5 项 RCT 中为标准治疗,在 5 项 RCT 中为安慰剂。8 项 RCT 中 COVID-19 疾病严重程度为轻度,1 项为中度,1 项为轻度和中度。与对照组相比,IVM 并未降低全因死亡率(相对风险[RR],0.37[95%置信区间,0.12-1.13];极低 QoE)或 LOS(平均差值,0.72 天[95%置信区间,-0.86 至 2.29 天];极低 QoE)。IVM 与对照组之间的 AE、SAE 和病毒清除率相似(所有结局的 QoE 为低)。按 COVID-19 严重程度或 RoB 进行的亚组分析与主要分析基本一致;3 项 RoB 较高的 RCT 中,IVM 降低了全因死亡率。
与标准治疗或安慰剂相比,IVM 并未降低 COVID-19 患者中 RCT 中全因死亡率、LOS 或病毒清除率。IVM 对 AE 或 SAE 没有影响,也不是治疗 COVID-19 患者的可行选择。