Anticoagulation Strategies in Non-Critically Ill Patients with Covid-19.
Рандомизированное исследованиеСтатьяAdaptive Clinical TrialПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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McQuilten Zoe K, Venkatesh Balasubramanian, Jha Vivekanand, Roberts Jason, Morpeth Susan C, Totterdell James A, McPhee Grace M, Abraham John, Bam Niraj, Bandara Methma, Bangi Ashpak K, Barina Lauren A, Basnet Bhupendra K, Bhally Hasan, Bhusal Khema R, Bogati Umesh, Bowen Asha C, Burke Andrew J, Christopher Devasahayam J, Chunilal Sanjeev D, Cochrane Belinda, Curnow Jennifer L, Das Santa Kumar, Dhungana Ashesh, Di Tanna Gian Luca, Dotel Ravindra, DSouza Hyjel, Dummer Jack, Dutta Sourabh, Foo Hong, Gilbey Timothy L, Giles Michelle L, Goli Kasiram, Gordon Adrienne, Gyanwali Pradip, Haksar Dipak, Hudson Bernard J, Jani Manoj K, Jevaji Purnima R, Jhawar Sachin, Jindal Aikaj, John M Joseph, John Mary, John Flavita B, John Oommen, Jones Mark, Joshi Rajesh D, Kamath Prashanthi, Kang Gagandeep, Karki Achyut R, Karmalkar Abhishek M, Kaur Baldeep, Koganti Kalyan Chakravarthy, Koshy Jency M, Krishnamurthy Mathew S, Lau Jillian S, Lewin Sharon R, Lim Lyn-Li, Marschner Ian C, Marsh Julie A, Maze Michael J, McGree James M, McMahon James H, Medcalf Robert L, Merriman Eileen G, Misal Amol P, Mora Jocelyn M, Mudaliar Vijaybabu K, Nguyen Vi, O'Sullivan Matthew V, Pant Suman, Pant Pankaj, Paterson David L, Price David J, Rees Megan A, Robinson James O, Rogers Benjamin A, Samuel Sandhya, Sasadeusz Joe, Sharma Deepak, Sharma Prabhat K, Shrestha Roshan, Shrestha Sailesh K, Shrestha Prajowl, Shukla Urvi, Shum Omar, Sommerville Christine, Spelman Tim, Sullivan Richard P, Thatavarthi Umashankar, Tran Huyen A, Trask Nanette, Whitehead Clare L, Mahar Robert K, Hammond Naomi E, McFadyen James D, Snelling Thomas L, Davis Joshua S, Denholm Justin T, Tong Steven Y C
Аннотация
BACKGROUND: Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS: In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints. RESULTS: Between February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n=1273; Australia and New Zealand, n=138; and Nepal, n=115), the primary outcome occurred in 35 (5.9%) of 596 in low-dose, 25 (4.2%) of 601 in intermediate-dose, 20 (7.2%) of 279 in low-dose plus aspirin, and 7 (14%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratio<1; Pr], 86%), for low-dose plus aspirin 0.88 (95% CrI, 0.47 to 1.64; Pr, 65%), and for therapeutic-dose anticoagulation 2.22 (95% CrI, 0.77 to 6.20; Pr, 7%). Overall thrombotic and bleeding rates were 0.8% and 0.4%, respectively. There were 10 serious adverse reactions related to anticoagulation strategy, of which nine were grade 1 or 2 across study interventions and one grade 4 episode of retroperitoneal hematoma in a patient receiving intermediate-dose anticoagulation. CONCLUSIONS: In hospitalized non–critically ill adults with Covid-19, compared with low-dose, there was an 86% posterior probability that intermediate-dose, 65% posterior probability that low-dose plus aspirin, and a 7% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions. (Funded by Australian National Health and Medical Research Council or Medical Research Future Fund Investigator and Practitioner Grants and others; ClinicalTrials.gov number, NCT04483960.)