二甲双胍、伊维菌素和氟伏沙明治疗 COVID-19 的随机试验。
Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.
机构信息
From the Departments of Medicine (C.T.B., N.E.I., K.M.H., A.A.H., B.P., S.L.F., N.A., N.V.R., S.M.E., H.G.S., M.F.P., D.R.B.) and Surgery (C.J.T., N.R.K.), Emergency Medicine (M.A.P., M.B.), and Laboratory Medicine and Pathology (A.B.K.), Medical School, the Divisions of Biostatistics (J.D.H., J.L.P., L.K.S., V.R., S. Lindberg, T.A.M.) and Epidemiology and Community Health (N.E.S.), School of Public Health, and the Department of Biomedical Engineering (D.J.O.), University of Minnesota, the Department of Emergency Medicine, Hennepin County Medical Center (M.A.P., W.J.T., M.B.), and the Investigational Drug Service Pharmacy, University of Minnesota-Fairview (D.G.L.), Minneapolis, and UnitedHealth Group, Optum Labs, Minnetonka (K.C.) - all in Minnesota; the Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill (J.B.B.); the Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (D.M.L., R.F., S. Lee); the Department of Medicine, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora (J.M.N., A.Z.); the Department of Medicine, Olive View-University of California, Los Angeles (H.K.B.); Atlanta Veterans Affairs Medical Center and the Department of Medicine, Emory University School of Medicine - both in Atlanta (B.A.); and the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville (J.L.T.).
出版信息
N Engl J Med. 2022 Aug 18;387(7):599-610. doi: 10.1056/NEJMoa2201662.
BACKGROUND
Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.
METHODS
In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications.
RESULTS
A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine.
CONCLUSIONS
None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).
背景
早期治疗以预防严重的 2019 年冠状病毒病（COVID-19）是应对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）大流行的综合措施的重要组成部分。
方法
在这项 3 期、双盲、随机、安慰剂对照试验中，我们采用 2×3 析因设计来检验三种已重新用于临床的药物（二甲双胍、伊维菌素和氟伏沙明）在预防已确诊感染 SARS-CoV-2 且症状出现后 3 天内入组且不到 7 天的非住院成人发生严重 SARS-CoV-2 感染方面的有效性。患者年龄在 30 至 85 岁之间，均超重或肥胖。主要复合终点为低氧血症（家庭血氧仪上的血氧饱和度≤93%）、急诊就诊、住院或死亡。所有分析均使用同时接受随机分组且校正了 SARS-CoV-2 疫苗接种和其他试验药物使用的对照。
结果
共有 1431 名患者接受了随机分组；其中 1323 名患者被纳入主要分析。患者的中位年龄为 46 岁；56%为女性（其中 6%为孕妇），52%已接种疫苗。二甲双胍的主要事件调整后比值比为 0.84（95%置信区间[CI]，0.66 至 1.09；P=0.19），伊维菌素为 1.05（95% CI，0.76 至 1.45；P=0.78），氟伏沙明为 0.94（95% CI，0.66 至 1.36；P=0.75）。在预先设定的次要分析中，二甲双胍的急诊就诊、住院或死亡调整后比值比为 0.58（95% CI，0.35 至 0.94），伊维菌素为 1.39（95% CI，0.72 至 2.69），氟伏沙明为 1.17（95% CI，0.57 至 2.40）。二甲双胍的住院或死亡调整后比值比为 0.47（95% CI，0.20 至 1.11），伊维菌素为 0.73（95% CI，0.19 至 2.77），氟伏沙明为 1.11（95% CI，0.33 至 3.76）。
结论
评估的三种药物均未能预防 COVID-19 相关的低氧血症、急诊就诊、住院或死亡的发生。（由 Parsemus 基金会等资助；COVID-OUT ClinicalTrials.gov 编号，NCT04510194。）
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