Department of Clinical Development, Bill & Melinda Gates Medical Research Institute, Cambridge, Massachusetts, USA.
Department of Allergy, Asthma and Clinical Research, Science 37, Los Angeles, California, USA.
Clin Infect Dis. 2022 Aug 24;75(1):e473-e481. doi: 10.1093/cid/ciab813.
Severe acute respiratory syndrome coronavirus 2 infection may be associated with a prothrombotic state, predisposing patients for a progressive disease course. We investigated whether rivaroxaban, a direct oral anticoagulant factor Xa inhibitor, would reduce coronavirus disease 2019 (COVID-19) progression.
Adults (N = 497) with mild COVID-19 symptoms and at high risk for COVID-19 progression based on age, body mass index, or comorbidity were randomized 1:1 to either daily oral rivaroxaban 10 mg (N = 246) or placebo equivalent (N = 251) for 21 days and followed to day 35. Primary end points were safety and progression. Absolute difference in progression risk was assessed using a stratified Miettinen and Nurminen method.
The study was terminated after 497 of the target 600 participants were enrolled due to a prespecified interim analysis of the first 200 participants that crossed the futility boundary for the primary efficacy end point in the intent-to-treat population. Enrollees were 85% aged <65 years; 60% female; 27% Hispanic, Black, or other minorities; and 69% with ≥2 comorbidities. Rivaroxaban was well tolerated. Disease progression rates were 46 of 222 (20.7%) in rivaroxaban vs 44 of 222 (19.8%) in placebo groups, with a risk difference of -1.0 (95% confidence interval, -6.4 to 8.4; P = .78).
We did not demonstrate an impact of rivaroxaban on disease progression in high-risk adults with mild COVID-19. There remains a critical public health gap in identifying scalable effective therapies for high-risk people in the outpatient setting to prevent COVID-19 progression.
严重急性呼吸综合征冠状病毒 2 感染可能与血栓前状态有关，使患者疾病进展。我们研究了直接口服抗凝药 Xa 因子抑制剂利伐沙班是否会降低 2019 年冠状病毒病（COVID-19）的进展。
497 名患有轻度 COVID-19 症状且基于年龄、体重指数或合并症处于 COVID-19 进展高风险的成年人，被随机分为 1:1 接受每日口服利伐沙班 10mg（N=246）或安慰剂（N=251），共 21 天，并随访至第 35 天。主要终点为安全性和进展。使用分层 Miettinen 和 Nurminen 方法评估进展风险的绝对差异。
由于前 200 名参与者的预设中期分析跨越了意向治疗人群中主要疗效终点的无效边界，因此在纳入了 600 名目标参与者中的 497 名后，研究提前终止。纳入的参与者 85%年龄<65 岁；60%为女性；27%为西班牙裔、黑人或其他少数族裔；69%有≥2 种合并症。利伐沙班耐受良好。利伐沙班组的疾病进展率为 222 例中的 46 例（20.7%），安慰剂组为 222 例中的 44 例（19.8%），风险差异为-1.0（95%置信区间，-6.4 至 8.4；P=0.78）。
我们没有发现利伐沙班对患有轻度 COVID-19 的高危成年人疾病进展有影响。在识别适合高危人群的可扩展有效疗法以预防 COVID-19 进展方面，仍然存在重大的公共卫生差距。
