Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.
Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.
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DOI：
10.1056/nejmoa2023184
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发表时间：
2021-02-11
期刊：
影响因子：
--
通讯作者：
Swaminathan S
中科院分区：
文献类型：
--
作者：
WHO Solidarity Trial Consortium;Pan H;Peto R;Henao-Restrepo AM;Preziosi MP;Sathiyamoorthy V;Abdool Karim Q;Alejandria MM;Hernández García C;Kieny MP;Malekzadeh R;Murthy S;Reddy KS;Roses Periago M;Abi Hanna P;Ader F;Al-Bader AM;Alhasawi A;Allum E;Alotaibi A;Alvarez-Moreno CA;Appadoo S;Asiri A;Aukrust P;Barratt-Due A;Bellani S;Branca M;Cappel-Porter HBC;Cerrato N;Chow TS;Como N;Eustace J;García PJ;Godbole S;Gotuzzo E;Griskevicius L;Hamra R;Hassan M;Hassany M;Hutton D;Irmansyah I;Jancoriene L;Kirwan J;Kumar S;Lennon P;Lopardo G;Lydon P;Magrini N;Maguire T;Manevska S;Manuel O;McGinty S;Medina MT;Mesa Rubio ML;Miranda-Montoya MC;Nel J;Nunes EP;Perola M;Portolés A;Rasmin MR;Raza A;Rees H;Reges PPS;Rogers CA;Salami K;Salvadori MI;Sinani N;Sterne JAC;Stevanovikj M;Tacconelli E;Tikkinen KAO;Trelle S;Zaid H;Røttingen JA;Swaminathan S
世界卫生组织专家组建议在2019年因冠状病毒病住院的患者中进行四种重新使用的抗病毒药物--瑞德西韦、羟氯喹、洛匹那韦和干扰素β-1a--的死亡率试验。我们将新冠肺炎住院患者随机平均分配到当地可用的一种试验药物方案和开放对照（最多五种选择，四种活性药物和当地标准治疗）之间。意向性治疗主要分析检查了每种试验药物及其对照（药物可用，但患者分配到相同的治疗，但不使用该药物）的4个成对比较中的住院死亡率。根据年龄和试验入组时机械通气状态分层计算死亡率比。在30个国家的405家医院中，11，330名成人接受随机分组; 2750名被分配接受Remdesivir，954名接受羟氯喹，1411名接受Lopinavir（无干扰素），2063名接受干扰素（包括651名干扰素加Lopinavir），4088名不接受试验药物。治疗中途的依从性为94 - 96%，交叉为2 - 6%。总共报告了1253例死亡（中位死亡日，第8天;四分位数范围，4 - 14）。Kaplan-Meier 28天死亡率为11.8%（如果患者在随机化时已接受通气，则为39.0%，否则为9.5%）。2743名接受Remdesivir治疗的患者中有301人死亡，2708名接受其对照的患者中有303人死亡（率比，0.95; 95%置信区间[CI]，0.81 - 1.11; P=0.50），947例接受羟氯喹治疗的患者中有104例，906例接受对照组的84例（率比，1.19; 95%CI，0.89 - 1.59; P=0.23），1399例接受洛匹那韦治疗的患者中有148例，1372例接受对照组的患者中有146例（率比，1.00; 95%CI，0.79 - 1.25; P=0.97），2050例接受干扰素治疗的患者中有243例，2050例接受对照组的216例（率比，1.16; 95% CI，0.96 - 1.39; P=0.11）。没有任何药物能明确降低总体或任何亚组的死亡率，或减少通气开始时间或住院时间。根据总体死亡率、开始通气时间和住院时间，这些瑞德西韦、羟氯喹、洛匹那韦和干扰素方案对新冠肺炎住院患者的影响很小或没有影响。（由世界卫生组织资助; ISRCTN注册号：ISRCTN 83971151; ClinicalTrials.gov编号：NCT 04315948）
World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)