Tobias Tritschler1,2, Marie-Eve Mathieu1, Leslie Skeith3, Marc Rodger4, Saskia Middeldorp5, Timothy Brighton6, Per Morten Sandset7, Susan R Kahn4,8, Derek C Angus9, Marc Blondon10, Marc J Bonten11, Marco Cattaneo12, Mary Cushman13, Lennie P G Derde11,14, Maria T DeSancho15, Jean-Luc Diehl16,17, Ewan Goligher18,19, Bernd Jilma20, Peter Jüni21,22, Patrick R Lawler23,24,25, Marco Marietta26, John C Marshall27, Colin McArthur28, Carlos Henrique Miranda29, Tristan Mirault17,30,31, Nuccia Morici32, Usha Perepu33, Christian Schörgenhofer20, Michelle Sholzberg34, Alex C Spyropoulos35, Steve A Webb36, Ryan Zarychanski37,38, Stéphane Zuily39, Grégoire Le Gal1. 1. Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. 2. Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 3. Department of Medicine, University of Calgary, Calgary, AB, Canada. 4. Department of Medicine, McGill University, Montreal, QC, Canada. 5. Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. 6. Department of Haematology, New South Wales Health Pathology Randwick, Prince of Wales Hospital, Sydney, NSW, Australia. 7. Department of Haematology, Oslo University Hospital and University of Oslo, Oslo, Norway. 8. Divisions of Internal Medicine and Clinical Epidemiology, Jewish General Hospital/Lady Davis Institute, Montreal, QC, Canada. 9. University of Pittsburgh and UPMC Health System, Pittsburgh, PA, USA. 10. Division of Angiology and Haemostasis, Faculty of Medicine and Geneva University Hospitals, Geneva, Switzerland. 11. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. 12. Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy. 13. Departments of Medicine and Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA. 14. Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 15. Division of Hematology-Oncology, Department of Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA. 16. Service de Médecine Intensive - Réanimation, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, Paris, France. 17. Innovative Therapies in Haemostasis, INSERM UMR-S1140, Paris University, Paris, France. 18. Interdivisional Department of Critical Care, University of Toronto, Toronto, ON, Canada. 19. Division of Respirology, Department of Medicine, University Health Network, Toronto, ON, Canada. 20. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. 21. Applied Health Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada. 22. Department of Medicine and Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada. 23. Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada. 24. Ted Rogers Centre for Heart Research, Toronto, ON, Canada. 25. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. 26. Dipartimento Oncologia ed Ematologia, Azienda Ospedaliero-Universitaria di Modena, Ospedale Policlinico, Modena, Italy. 27. Department of Critical Care Medicine, St Michael's Hospital, Toronto, ON, Canada. 28. Auckland City Hospital, Intensive Care, Auckland, New Zealand. 29. Division of Emergency Medicine, Department of Internal Medicine, Ribeirão Preto School of Medicine, São Paulo University, Ribeirão Preto, Brazil. 30. PARCC, INSERM U970, Paris, France. 31. Hôpital Européen Georges-Pompidou, Assistance Publique - Hôpitaux de Paris, Paris, France. 32. Intensive Cardiac Care Unit and De Gasperis Cardio Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 33. Department of Internal Medicine, University of Iowa, Iowa City, IA, USA. 34. St. Michael's Hospital and Departments of Medicine, and Laboratory Medicine and Pathobiology, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, ON, Canada. 35. Feinstein Institutes for Medical Research and The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, and Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell Health at Lenox Hill Hospital, New York, NY, USA. 36. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 37. Department of Internal Medicine, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada. 38. Cancer Care Manitoba, Research Institute of Oncology and Haematology, Winnipeg, MB, Canada. 39. Vascular Medicine Division and Regional Competence Center for Marfan Syndrome, Inserm, DCAC and CHRU-Nancy, Université de Lorraine, Nancy, France.
Abstract
INTRODUCTION: Coronavirus disease (COVID-19) is associated with a high incidence of thrombosis and mortality despite standard anticoagulant thromboprophylaxis. There is equipoise regarding the optimal dose of anticoagulant intervention in hospitalized patients with COVID-19 and consequently, immediate answers from high-quality randomized trials are needed. METHODS: The World Health Organization's International Clinical Trials Registry Platform was searched on June 17, 2020 for randomized controlled trials comparing increased dose to standard dose anticoagulant interventions in hospitalized COVID-19 patients. Two authors independently screened the full records for eligibility and extracted data in duplicate. RESULTS: A total of 20 trials were included in the review. All trials are open label, 5 trials use an adaptive design, 1 trial uses a factorial design, 2 trials combine multi-arm parallel group and factorial designs in flexible platform trials, and at least 15 trials have multiple study sites. With individual target sample sizes ranging from 30 to 3000 participants, the pooled sample size of all included trials is 12 568 participants. Two trials include only intensive care unit patients, and 10 trials base patient eligibility on elevated D-dimer levels. Therapeutic intensity anticoagulation is evaluated in 14 trials. All-cause mortality is part of the primary outcome in 14 trials. DISCUSSION: Several trials evaluate different dose regimens of anticoagulant interventions in hospitalized patients with COVID-19. Because these trials compete for sites and study participants, a collaborative effort is needed to complete trials faster, conduct pooled analyses and bring effective interventions to patients more quickly.
INTRODUCTION:Coronavirus disease (COVID-19) is associated with a high incidence of thrombosis and mortality despite standard anticoagulant thromboprophylaxis. There is equipoise regarding the optimal dose of anticoagulant intervention in hospitalized patients with COVID-19 and consequently, immediate answers from high-quality randomized trials are needed. METHODS: The World Health Organization's International Clinical Trials Registry Platform was searched on June 17, 2020 for randomized controlled trials comparing increased dose to standard dose anticoagulant interventions in hospitalized COVID-19patients. Two authors independently screened the full records for eligibility and extracted data in duplicate. RESULTS: A total of 20 trials were included in the review. All trials are open label, 5 trials use an adaptive design, 1 trial uses a factorial design, 2 trials combine multi-arm parallel group and factorial designs in flexible platform trials, and at least 15 trials have multiple study sites. With individual target sample sizes ranging from 30 to 3000 participants, the pooled sample size of all included trials is 12 568 participants. Two trials include only intensive care unit patients, and 10 trials base patient eligibility on elevated D-dimer levels. Therapeutic intensity anticoagulation is evaluated in 14 trials. All-cause mortality is part of the primary outcome in 14 trials. DISCUSSION: Several trials evaluate different dose regimens of anticoagulant interventions in hospitalized patients with COVID-19. Because these trials compete for sites and study participants, a collaborative effort is needed to complete trials faster, conduct pooled analyses and bring effective interventions to patients more quickly.
Authors: Ba Pham; Patricia Rios; Amruta Radhakrishnan; Nazia Darvesh; Jesmin Antony; Chantal Williams; Naveeta Ramkissoon; Gordon V Cormack; Maura R Grossman; Melissa Kampman; Milan Patel; Fatemeh Yazdi; Reid Robson; Marco Ghassemi; Erin Macdonald; Rachel Warren; Matthew P Muller; Sharon E Straus; Andrea C Tricco Journal: BMJ Open Date: 2022-06-03 Impact factor: 3.006
Authors: José Augusto Santos Pellegrini; Tatiana Helena Rech; Patrícia Schwarz; Ana Cláudia Tonelli de Oliveira; Tarsila Vieceli; Rafael Barberena Moraes; Leo Sekine; Marina Verçoza Viana Journal: J Thromb Thrombolysis Date: 2021-02-18 Impact factor: 2.300
Authors: Stuart L Cohen; Eugenia Gianos; Mathew A Barish; Saurav Chatterjee; Nina Kohn; Martin Lesser; Dimitrios Giannis; Kevin Coppa; Jamie S Hirsch; Thomas G McGinn; Mark E Goldin; Alex C Spyropoulos Journal: Thromb Haemost Date: 2022-03-11 Impact factor: 6.681