Objective To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19. Design CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. Setting 17 hospital sites in India and Australia. Participants Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19. Intervention Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days. Main outcome measures The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population. Results Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met. Conclusions In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan. Trial registration ClinicalTrials.gov [NCT04394117][1]. The final dataset will be under the custodianship of the chair of the trial steering committee. all individual participant data that are collected during the trial will be de-identified. The researchers intend de-identified data will contribute to global learnings through an appropriately constituted individual participant data level collaboration. Requests for data access or analysis proposals will be reviewed by the trial steering committee, who will assess proposals according to criteria based on scientific merit and contribution to global knowledge. Data sharing will be performed in compliance with local data protection laws. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04394117&atom=%2Fbmj%2F379%2Fbmj-2022-072175.atom

中文翻译：

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用于治疗 covid-19 的血管紧张素受体阻滞剂：实用、适应性、多中心、3 期、随机对照试验

目的 确定用血管紧张素受体阻滞剂破坏肾素血管紧张素系统是否会改善 covid-19 患者的临床结果。设计 CLARITY 是一项务实的、适应性的、多中心的 3 期随机对照试验。在印度和澳大利亚设置 17 个医院站点。参与者参与者年龄至少为 18 岁，之前未接受过血管紧张素受体阻滞剂治疗，经实验室确诊为严重急性呼吸系统综合症冠状病毒-2 (SARS-CoV-2) 感染，已入院治疗 covid-19。干预 口服血管紧张素受体阻滞剂（印度的替米沙坦）或安慰剂 (1:1) 28 天。主要结果指标主要终点是在第 14 天使用修改后的世界卫生组织临床进展量表（WHO 量表）的 covid-19 疾病严重程度。次要结果是第 28 天的 WHO 量表评分、死亡率、入住重症监护室和呼吸衰竭。在意向性治疗人群中按顺序评估分析。结果 2020 年 5 月 3 日至 2021 年 11 月 13 日期间，对 2930 人进行了资格筛选，其中 393 人被随机分配到血管紧张素受体阻滞剂组（其中 388 人（98.7%）分配到替米沙坦 40 mg/天），394 人被分配到对照组。787 名参与者被随机分组​​：778 名 (98.9%) 来自印度，9 名 (1.1%) 来自澳大利亚。在分配血管紧张素受体阻滞剂的 384 名参与者中，第 14 天的 WHO 量表评分中位数为 1（四分位数范围 1-1），在分配安慰剂的 382 名参与者中为 1（1-1）（调整后的比值比 1.51（95% 可信区间 1.02 至 2.23） ，比值比 >1 的概率 (Pr(OR>1)=0.98)。第 28 天的 WHO 量表评分几乎没有显示出组间差异的证据（1.02（0.55 至 1.87），Pr(OR>1)=0.53）。当满足预先指定的无效规则时，试验停止。结论 在因 covid-19 入院的患者中，大多数患有轻度疾病，不需要氧气，根据疾病严重程度评分，没有发现血管紧张素受体阻滞剂治疗有益的证据，主要使用 40 mg/天的替米沙坦。试验注册 ClinicalTrials.gov [NCT04394117][1]。最终数据集将由试验指导委员会主席保管。在试验期间收集的所有个体参与者数据都将被去识别化。研究人员打算通过适当构成的个人参与者数据级协作，去识别化的数据将有助于全球学习。数据访问或分析提案的请求将由试验指导委员会审查，他们将根据基于科学价值和对全球知识的贡献的标准评估提案。数据共享将按照当地数据保护法进行。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04394117&atom=%2Fbmj%2F379%2Fbmj-2022-072175.atom 数据共享将按照当地数据保护法进行。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04394117&atom=%2Fbmj%2F379%2Fbmj-2022-072175.atom 数据共享将按照当地数据保护法进行。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04394117&atom=%2Fbmj%2F379%2Fbmj-2022-072175.atom