Eikelboom John, Rangarajan Sumathy, Jolly Sanjit S, Belley-Cote Emilie P, Whitlock Richard, Beresh Heather, Lewis Gayle, Xu Lizhen, Chan Noel, Bangdiwala Shrikant, Diaz Rafael, Orlandini Andres, Hassany Mohamed, Tarhuni Wadea M, Yusufali A M, Sharma Sanjib Kumar, Kontsevaya Anna, Lopez-Jaramillo Patricio, Avezum Alvaro, Dans Antonio L, Wasserman Sean, Felix Camilo, Kazmi Khawar, Pais Prem, Xavier Denis, Lopes Renato D, Berwanger Otavio, Nkeshimana Menelas, Harper William, Loeb Mark, Choudhri Shurjeel, Farkouh Michael E, Bosch Jackie, Anand Sonia S, Yusuf Salim
Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
CJC Open. 2022 Jun;4(6):568-576. doi: 10.1016/j.cjco.2022.02.010. Epub 2022 Mar 1.
Effective treatments for COVID-19 are urgently needed, but conducting randomized trials during the pandemic has been challenging.
The Anti-Coronavirus Therapy (ACT) trials are parallel factorial international trials that aimed to enroll 3500 outpatients and 2500 inpatients with symptomatic COVID-19. The outpatient trial is evaluating colchicine vs usual care, and aspirin vs usual care. The primary outcome for the colchicine randomization is hospitalization or death, and for the aspirin randomization, it is major thrombosis, hospitalization, or death. The inpatient trial is evaluating colchicine vs usual care, and the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily vs usual care. The primary outcome for the colchicine randomization is need for high-flow oxygen, need for mechanical ventilation, or death, and for the rivaroxaban plus aspirin randomization, it is major thrombotic events, need for high-flow oxygen, need for mechanical ventilation, or death.
At the completion of enrollment on February 10, 2022, the outpatient trial had enrolled 3917 patients, and the inpatient trial had enrolled 2611 patients. Challenges encountered included lack of preliminary data about the interventions under evaluation, uncertainties related to the expected event rates, delays in regulatory and ethics approvals, and in obtaining study interventions, as well as the changing pattern of the COVID-19 pandemic.
The ACT trials will determine the efficacy of anti-inflammatory therapy with colchicine, and antithrombotic therapy with aspirin given alone or in combination with rivaroxaban, across the spectrum of mild, moderate, and severe COVID-19. Lessons learned from the conduct of these trials will inform planning of future trials.
迫切需要针对2019冠状病毒病（COVID-19）的有效治疗方法，但在疫情期间开展随机试验具有挑战性。
抗冠状病毒治疗（ACT）试验是平行析因国际试验，旨在招募3500例有症状的COVID-19门诊患者和2500例住院患者。门诊试验正在评估秋水仙碱与常规治疗，以及阿司匹林与常规治疗。秋水仙碱随机分组的主要结局是住院或死亡，阿司匹林随机分组的主要结局是重大血栓形成、住院或死亡。住院试验正在评估秋水仙碱与常规治疗，以及每日两次服用2.5毫克利伐沙班和每日一次服用100毫克阿司匹林的联合用药与常规治疗。秋水仙碱随机分组的主要结局是需要高流量吸氧、需要机械通气或死亡，利伐沙班加阿司匹林随机分组的主要结局是重大血栓事件、需要高流量吸氧、需要机械通气或死亡。
在2022年2月10日完成入组时，门诊试验已招募3917例患者，住院试验已招募2611例患者。遇到的挑战包括缺乏关于所评估干预措施的初步数据、与预期事件发生率相关的不确定性、监管和伦理审批延迟以及获取研究干预措施方面的延迟，以及COVID-19疫情模式的变化。
ACT试验将确定在轻、中、重度COVID-19范围内，秋水仙碱抗炎治疗以及单独使用阿司匹林或与利伐沙班联合使用的抗血栓治疗的疗效。从这些试验的开展中吸取的经验教训将为未来试验的规划提供参考。
