Importance Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration ClinicalTrials.gov Identifier: NCT04505774.

中文翻译：

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P2Y12 抑制剂对非重症住院 COVID-19 患者无器官支持生存的影响：一项随机临床试验。

重要性 血小板是改善 COVID-19 患者临床结果的潜在治疗靶点。目的 评估因 COVID-19 住院的非危重患者抗凝治疗中添加 P2Y12 抑制剂的益处和风险。设计、设置和参与者 2021 年 2 月至 2021 年 6 月期间，在巴西、意大利、西班牙和美国的 60 家医院进行了一项开放标签、贝叶斯、适应性随机临床试验，纳入了 562 名因 COVID-19 住院的非重症患者。最终 90 天随访日期为 2021 年 9 月 15 日。 干预措施 患者被随机分配至治疗剂量的肝素加 P2Y12 抑制剂 (n = 293) 或仅治疗剂量的肝素（常规护理）(n = 269) ）以 1:1 的比例持续 14 天或直至出院，以较早者为准。替格瑞洛是首选的 P2Y12 抑制剂。主要结果和措施 复合主要结果是按顺序量表评估的无器官支持天数，该量表结合了院内死亡（指定值为 -1）以及对于存活出院的患者而言，无呼吸系统支持的天数或心血管器官支持直至指数住院第 21 天（范围为 -1 至 21 天；分数越高表示器官支持越少，结果越好）。主要安全性结局是国际血栓与止血学会定义的 28 天大出血。结果 当满足预先设定的无效标准时，停止非危重症患者的入组。所有 562 名随机分组患者（平均年龄 52.7 [SD，13.5] 岁；41.5% 为女性）完成了试验，87% 在研究第 1 天结束时接受了治疗剂量的肝素。在 P2Y12 抑制剂组中，替格瑞洛63% 的患者使用氯吡格雷，37% 的患者使用氯吡格雷。P2Y12 抑制剂组患者的无器官支持天数中位数为 21 天（IQR，20-21 天），常规护理组患者为 21 天（IQR，21-21 天）（调整后比值比，0.83） [95% 可信区间，0.55-1.25]；无效的后验概率 [定义为比值比 <1.2]，96%）。P2Y12 抑制剂组有 6 名患者 (2.0%) 发生大出血，常规护理组有 2 名患者 (0.7%) 发生大出血（调整后比值比，3.31 [95% CI，0.64-17.2]；P = .15）。结论和相关性 在因 COVID-19 住院的非危重患者中，与仅使用治疗剂量的肝素相比，在治疗剂量的肝素基础上使用 P2Y12 抑制剂并未导致器官改善的几率增加住院期间 21 天内无支持的天数。试验注册 ClinicalTrials.gov 标识符：NCT04505774。