Data_Sheet_1_An Open Label Trial to Assess Safety of Losartan for Treating Worsening Respiratory Illness in COVID-19.PDF

Rationale: Coronavirus disease 2019 (COVID-19) can cause disruption of the renin-angiotensin system in the lungs, possibly contributing to pulmonary capillary leakage. Thus, angiotensin receptor blockers (ARBs) may improve respiratory failure.
Objective: Assess safety of losartan for use in respiratory failure related to COVID-19 (NCT04335123).
Methods: Single arm, open label trial of losartan in those hospitalized with respiratory failure related to COVID-19. Oral losartan (25 mg daily for 3 days, then 50 mg) was administered from enrollment until day 14 or hospital discharge. A post-hoc external control group with patients who met all inclusion criteria was matched 1:1 to the treatment group using propensity scores for comparison.
Measures: Primary outcome was cumulative incidence of any adverse events. Secondary, explorative endpoints included measures of respiratory failure, length of stay and vital status.
Results: Of the 34 participants enrolled in the trial, 30 completed the study with a mean age SD of 53.8 ± 17.7 years and 17 males (57%). On losartan, 24/30 (80%) experienced an adverse event as opposed to 29/30 (97%) of controls, with a lower average number of adverse events on losartan relative to control (2.2 vs. 3.3). Using Poisson regression and controlling for age, sex, race, date of enrollment, disease severity at enrollment, and history of high-risk comorbidities, the incidence rate ratio of adverse events on losartan relative to control was 0.69 (95% CI: 0.49–0.97)
Conclusions: Losartan appeared safe for COVID-19-related acute respiratory compromise. To assess true efficacy, randomized trials are needed.

研究背景：2019冠状病毒病（Coronavirus disease 2019, COVID-19）可引发肺部肾素-血管紧张素系统（renin-angiotensin system）紊乱，可能导致肺毛细血管渗漏。因此，血管紧张素受体拮抗剂（angiotensin receptor blockers, ARBs）或可改善呼吸衰竭。
研究目的：评估氯沙坦（losartan）用于治疗2019冠状病毒病相关呼吸衰竭的安全性（临床试验编号：NCT04335123）。
研究方法：本研究为单臂开放标签试验，纳入因2019冠状病毒病相关呼吸衰竭住院的患者。给药方案为口服氯沙坦：初始3日每日25mg，后续调整为每日50mg，从入组开始持续给药至第14天或患者出院。此外，我们设立事后外部对照组：选取符合全部纳入标准的患者，通过倾向得分（propensity scores）以1:1比例匹配治疗组进行对照比较。
评估指标：主要结局为任意不良事件的累积发生率；次要探索性终点包括呼吸衰竭相关指标、住院时长及生存状态。
研究结果：本试验共纳入34名受试者，其中30名完成研究，受试者平均年龄为53.8±17.7岁，男性17例（占比57%）。接受氯沙坦治疗的患者中，24/30（80%）出现不良事件，而对照组为29/30（97%）；治疗组平均不良事件数量低于对照组（2.2 vs 3.3）。经泊松回归（Poisson regression）校正年龄、性别、种族、入组日期、入组时疾病严重程度及高危合并症病史后，氯沙坦组相对于对照组的不良事件发生率比为0.69（95%置信区间：0.49–0.97）。
研究结论：氯沙坦用于治疗2019冠状病毒病相关急性呼吸功能不全的安全性良好。若要评估其真实疗效，仍需开展随机对照试验。