血小板是改善COVID-19患者临床预后的潜在治疗靶点。
评估因COVID-19住院的非危重患者在抗凝治疗中添加P2Y12抑制剂的益处和风险。
开放标签,贝叶斯,2021年2月至2021年6月,在巴西60家医院进行了纳入562名因COVID-19住院的非危重患者的适应性随机临床试验,意大利,西班牙,和美国。最后90天的随访日期是2021年9月15日。
患者以1:1的比例随机接受治疗剂量的肝素加P2Y12抑制剂(n=293)或仅接受治疗剂量的肝素(常规治疗)(n=269)治疗14天或直至出院。哪个更早。替格瑞洛是优选的P2Y12抑制剂。
复合主要结局是在序数量表上评估的无器官支持天数,结合住院死亡(赋值为-1)和,对于那些幸存下来出院的人来说,至住院指数第21天,无呼吸或心血管器官支持的天数(范围,-1至21天;得分越高表明器官支持越少,结果越好)。根据国际血栓形成和止血协会的定义,主要安全性结果是28天大出血。
当符合预设的无效性标准时,非危重患者的入选被终止。所有562例随机分组的患者(平均年龄,52.7[SD,13.5]年;41.5%的女性)完成了试验,87%的人在研究第1天结束时接受了治疗剂量的肝素。在P2Y12抑制剂组中,63%的患者使用替格瑞洛,37%的患者使用氯吡格雷.无器官支持天数的中位数为21天(IQR,20-21天)在P2Y12抑制剂组的患者中,为21天(IQR,21-21天)在常规护理组中(调整后的优势比,0.83[95%可信区间,0.55-1.25];徒劳的后验概率[定义为赔率比<1.2],96%)。P2Y12抑制剂组6例(2.0%)和常规治疗组2例(0.7%)发生大出血(调整比值比,3.31[95%CI,0.64-17.2];P=.15)。
在因COVID-19住院的非危重患者中,除了治疗剂量的肝素外,还使用P2Y12抑制剂,与仅治疗剂量的肝素相比,没有导致住院期间21天内无器官支持天数改善的几率增加.
ClinicalTrials.gov标识符:NCT04505774。
Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19.
To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19.
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.
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.
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.
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).
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.
ClinicalTrials.gov Identifier: NCT04505774.