Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies.
Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies.
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DOI：
10.1016/j.thromres.2020.09.027
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发表时间：
2020-12
影响因子：
7.5
通讯作者：
Sadeghipour P
中科院分区：
文献类型：
--
作者：
Bikdeli B;Talasaz AH;Rashidi F;Sharif-Kashani B;Farrokhpour M;Bakhshandeh H;Sezavar H;Dabbagh A;Beigmohammadi MT;Payandemehr P;Yadollahzadeh M;Riahi T;Khalili H;Jamalkhani S;Rezaeifar P;Abedini A;Lookzadeh S;Shahmirzaei S;Tahamtan O;Matin S;Amin A;Parhizgar SE;Jimenez D;Gupta A;Madhavan MV;Parikh SA;Monreal M;Hadavand N;Hajighasemi A;Maleki M;Sadeghian S;Mohebbi B;Piazza G;Kirtane AJ;Lip GYH;Krumholz HM;Goldhaber SZ;Sadeghipour P
微血管和大血管血栓形成事件是2019冠状病毒病（COVID-19）的标志之一。此外，旺盛的免疫反应被认为是COVID-19肺部和肺外表现的重要驱动因素。预防COVID-19重症患者血栓形成的最佳管理策略仍不清楚。COVID-19重症患者中中等剂量与标准剂量预防性抗凝治疗的比较：一项开放标签随机对照试验（INSPIRATION）和INSPIRATION-statin（INSPIRATION-S）研究在一项随机对照试验中采用2 × 2析因设计检验了两个独立假设。经逆转录聚合酶链反应确诊为COVID-19的住院重症患者将随机接受中等剂量与标准剂量预防性抗凝治疗。将对接受随机化的600例患者进行筛选，如果符合合格性标准，将进行额外的双盲分层随机化，接受阿托伐他汀20 mg每日一次与匹配安慰剂。将检验两种假设的主要终点的优效性，包括入组后30天内裁定的急性动脉血栓形成、静脉血栓栓塞（VTE）、体外膜肺氧合的使用或全因死亡的复合终点。关键次要终点包括全因死亡率、裁定的VTE和无呼吸机天数。关键安全性终点包括根据出血学术研究联盟定义的大出血和抗凝假设的重度血小板减少症（血小板计数<20，000/fL）。在预先规定的非劣效性次要分析中，考虑到基于比值比的非劣效性界值为1.8，本研究将检验中等强度与标准剂量抗凝治疗大出血的非劣效性。他汀类药物假设的关键安全性终点包括肝酶升高>3倍正常上限和临床诊断的肌病。主要分析将在改良的意向治疗人群中进行。将在关键亚组以及意向治疗和符合方案队列的探索性分析中检验结果。INSPIRATION和INSPIRATON-S研究将有助于解决COVID-19重症患者抗血栓治疗和血栓炎性治疗的临床相关问题。
Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.
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DOI：
10.15557/pimr.2020.0003
发表时间：
2020-01-01
影响因子：
3.6
作者：
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影响因子：
158.5
作者：
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影响因子：
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影响因子：
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Campbell, Robert A.
DOI：
10.1152/ajplung.00354.2004
发表时间：
2005-06-01
影响因子：
4.9
作者：
Jacobson, JR;Barnard, JW;Garcia, JGN
通讯作者：
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