Maia Israel S, Marcadenti Aline, Veiga Viviane C, Miranda Tamiris A, Gomes Samara P C, Carollo Mariana B S, Negrelli Karina L, Gomes Jackeline O, Tramujas Lucas, Abreu-Silva Erlon O, Westphal Glauco A, Fernandes Ruthy P, Horta Jacques G A, Oliveira Deborah C, Flato Uri A P, Paoliello Ricardo C R, Fernandes Camilo, Zandonai Cássio L, Coelho Juliana C, Barros Waldemar C, Lemos Juliana C, Bolan Renata S, Dutra Marcela M, Gebara Otavio C E, Lopes Ana T A, Alencar Filho Meton S, Arraes Jussara A, Hamamoto Victor A, Hernandes Mauro E, Golin Nicole A, Santos Tiago M, Santos Renato H N, Damiani Lucas P, Zampieri Fernando G, Gesto João, Machado Flávia R, Rosa Régis G, Azevedo Luciano C P, Avezum Alvaro, Lopes Renato D, Souza Thiago M L, Berwanger Otávio, Cavalcanti Alexandre B
HCor Research Institute, São Paulo, SP, Brazil.
ICU Nereu Ramos, Hospital Nereu Ramos, Florianópolis, SC, Brazil.
Lancet Reg Health Am. 2023 Apr;20:100466. doi: 10.1016/j.lana.2023.100466. Epub 2023 Mar 8.
Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering SARS-CoV2 viral load of COVID-19 patients.
REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087.
Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 [95% CI, -0.03 to 0.12], -0.02 [95% CI, -0.09 to 0.06], and -0.03 [95% CI, -0.11 to 0.04] for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups.
No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less.
Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13).
将已批准药物用于治疗新出现的疾病可能是一条有效的治疗捷径。我们旨在评估与安慰剂相比，重新利用的抗病毒药物在降低新冠病毒肺炎（COVID-19）患者的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒载量方面的疗效。
“REVOLUTIOn”是一项在巴西35个中心进行的随机、平行、双盲、多阶段、优效性和安慰剂对照的随机试验。我们纳入年龄在18岁及以上、因实验室确诊的SARS-CoV-2感染而住院、症状出现时间在9天以内且室内空气下血氧饱和度（SpO）为94%或更低的患者。所有参与者被随机分配接受阿扎那韦、达卡他韦或索磷布韦/达卡他韦或安慰剂治疗10天。主要结局是在意向性分析人群中评估的SARS-CoV-2病毒载量对数的衰减率（斜率）。该试验已在ClinicalTrials.gov注册，注册号为NCT04468087。
在2021年2月9日至2021年8月4日期间，共纳入255名参与者，并将其随机分配至阿扎那韦组（n = 64）、达卡他韦组（n = 66）、索磷布韦/达卡他韦组（n = 67）或安慰剂组（n = 58）。与安慰剂组相比，任何治疗组从基线到第10天的病毒载量对数变化均无显著差异（阿扎那韦组为0.05 [95%置信区间（CI），-0.03至0.12]，达卡他韦组为-0.02 [95% CI，-0.09至0.06]，索磷布韦/达卡他韦组为-0.03 [95% CI，-0.11至0.04]）。治疗组之间严重不良事件的发生率无显著差异。
在症状出现9天以内且需要吸氧支持的住院COVID-19患者中，与安慰剂相比，使用阿扎那韦、达卡他韦或索磷布韦/达卡他韦未观察到病毒载量有显著降低。
科学、技术和创新部（MCTI）-国家科学技术发展委员会（CNPQ）；拉丁美洲药品公司（Clamed）；H. Carlos Schneider工业公司（Ciser）；澳大利亚医院研究基金会；圣保罗HCór；布兰韦尔制药公司；奥斯瓦尔多·克鲁兹基金会（Fiocruz）的药物技术研究所（Farmanguinhos）；Fiocruz总体战略规划协调部（Cogeplan）；以及Fiocruz支持基金会（Fiotec，VPGDI-054-FIO-20-2-13）。
