Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
J Antimicrob Chemother. 2022 Sep 30;77(10):2706-2712. doi: 10.1093/jac/dkac266.
The COVER trial evaluated whether nitazoxanide or sofosbuvir/daclatasvir could lower the risk of SARS-CoV-2 infection. Nitazoxanide was selected given its favourable pharmacokinetics and in vitro antiviral effects against SARS-CoV-2. Sofosbuvir/daclatasvir had shown favourable results in early clinical trials.
In this clinical trial in Johannesburg, South Africa, healthcare workers and others at high risk of infection were randomized to 24 weeks of either nitazoxanide or sofosbuvir/daclatasvir as prevention, or standard prevention advice only. Participants were evaluated every 4 weeks for COVID-19 symptoms and had antibody and PCR testing. The primary endpoint was positive SARS-CoV-2 PCR and/or serology ≥7 days after randomization, regardless of symptoms. A Poisson regression model was used to estimate the incidence rate ratios of confirmed SARS-CoV-2 between each experimental arm and control.
Between December 2020 and January 2022, 828 participants were enrolled. COVID-19 infections were confirmed in 100 participants on nitazoxanide (2234 per 1000 person-years; 95% CI 1837-2718), 87 on sofosbuvir/daclatasvir (2125 per 1000 person-years; 95% CI 1722-2622) and 111 in the control arm (1849 per 1000 person-years; 95% CI 1535-2227). There were no significant differences in the primary endpoint between the treatment arms, and the results met the criteria for futility. In the safety analysis, the frequency of grade 3 or 4 adverse events was low and similar across arms.
In this randomized trial, nitazoxanide and sofosbuvir/daclatasvir had no significant preventative effect on infection with SARS-CoV-2 among healthcare workers and others at high risk of infection.
COVE 试验评估了硝唑尼特或索磷布韦/达卡他韦是否能降低 SARS-CoV-2 感染的风险。选择硝唑尼特是因为它具有良好的药代动力学特性和体外抗 SARS-CoV-2 的作用。索磷布韦/达卡他韦在早期临床试验中显示出良好的结果。
在这项在南非约翰内斯堡进行的临床试验中，医护人员和其他感染风险高的人被随机分配接受 24 周的硝唑尼特或索磷布韦/达卡他韦预防治疗，或仅接受标准预防建议。每 4 周评估一次参与者的 COVID-19 症状，并进行抗体和 PCR 检测。主要终点是随机分组后 7 天以上 SARS-CoV-2 PCR 和/或血清学阳性，无论有无症状。使用泊松回归模型估计每个实验组与对照组之间确诊 SARS-CoV-2 的发病率比。
2020 年 12 月至 2022 年 1 月期间，共纳入 828 名参与者。100 名参与者确诊为 COVID-19 感染，服用硝唑尼特（2234 人/年；95%CI 1837-2718），87 名服用索磷布韦/达卡他韦（2125 人/年；95%CI 1722-2622），111 名服用安慰剂（1849 人/年；95%CI 1535-2227）。治疗组之间在主要终点上无显著差异，结果符合无效标准。在安全性分析中，3 级或 4 级不良事件的频率较低，且各治疗组之间相似。
在这项随机试验中，硝唑尼特和索磷布韦/达卡他韦对医护人员和其他感染风险高的人群中 SARS-CoV-2 的感染没有显著的预防作用。
