Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.
Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.
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DOI：
10.1016/s0140-6736(21)02392-8
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发表时间：
2022-01-01
期刊：
影响因子：
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通讯作者：
MICHELLE investigators
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作者：
Ramacciotti E;Barile Agati L;Calderaro D;Aguiar VCR;Spyropoulos AC;de Oliveira CCC;Lins Dos Santos J;Volpiani GG;Sobreira ML;Joviliano EE;Bohatch Júnior MS;da Fonseca BAL;Ribeiro MS;Dusilek C;Itinose K;Sanches SMV;de Almeida Araujo Ramos K;de Moraes NF;Tierno PFGMM;de Oliveira ALML;Tachibana A;Chate RC;Santos MVB;de Menezes Cavalcante BB;Moreira RCR;Chang C;Tafur A;Fareed J;Lopes RD;MICHELLE investigators
因COVID-19住院的患者在出院后有发生血栓形成事件的风险;延长血栓预防在这一人群中的作用尚不清楚。在这项在巴西14个中心进行的开放标签、多中心、随机试验中，静脉血栓栓塞风险增加的COVID-19住院患者（静脉血栓栓塞国际医学预防登记[IMPROVE]静脉血栓栓塞[VTE]评分≥4或2-3，D-二聚体>500 ng/mL）在出院时被随机分配（1：1）接受利伐沙班10 mg/天或不抗凝治疗35天。意向性治疗分析的主要疗效结局为第35天时症状性或致死性静脉血栓栓塞、双侧下肢静脉超声和CT肺血管造影显示的无症状性静脉血栓栓塞、症状性动脉血栓栓塞和心血管死亡的复合终点。裁定设盲。主要安全性结局为大出血。在意向治疗人群中进行了主要和安全性分析。本试验注册于ClinicalTrials.gov，NCT 04662684。从2020年10月8日至2021年6月29日，筛选了997名患者。在这些患者中，677例不符合合格标准;其余320例患者入组并随机分配接受利伐沙班（n=160 [50%]）或无抗凝治疗（n=160 [50%]）。所有患者在住院期间均接受了标准剂量肝素的血栓预防。165例（52%）患者住院期间在重症监护室。197例（62%）患者的IMPROVE评分为2-3分，D-二聚体水平升高，121例（38%）评分为4分或以上。2例患者（每组各1例）因撤回知情同意而失访，未纳入意向治疗主要分析。159例分配接受利伐沙班的患者中有5例（3%）出现主要疗效结局，159例分配不接受抗凝治疗的患者中有15例（9%）出现主要疗效结局（相对风险0·33，95%CI 0·12-0·90; p=0·0293）。两个研究组均未发生大出血。利伐沙班组2例（1%）患者发生过敏反应。在因COVID-19住院后出院的高风险患者中，与未延长血栓预防相比，利伐沙班10 mg/天持续35天的血栓预防改善了临床结局。拜耳。
Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2–3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2–3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12–0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. Bayer.