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.
Original language | English |
---|---|
Pages (from-to) | 2958-2967 |
Number of pages | 10 |
Journal | Journal of Thrombosis and Haemostasis |
Volume | 18 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2020 |
Keywords
- anticoagulant
- COVID-19
- pulmonary embolism
- research networks
- thrombosis
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In: Journal of Thrombosis and Haemostasis, Vol. 18, No. 11, 11.2020, p. 2958-2967.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Anticoagulant interventions in hospitalized patients with COVID-19
T2 - A scoping review of randomized controlled trials and call for international collaboration
AU - Tritschler, Tobias
AU - Mathieu, Marie Eve
AU - Skeith, Leslie
AU - Rodger, Marc
AU - Middeldorp, Saskia
AU - Brighton, Timothy
AU - Sandset, Per Morten
AU - Kahn, Susan R.
AU - Angus, Derek C.
AU - Blondon, Marc
AU - Bonten, Marc J.
AU - Cattaneo, Marco
AU - Cushman, Mary
AU - Derde, Lennie P.G.
AU - DeSancho, Maria T.
AU - Diehl, Jean Luc
AU - Goligher, Ewan
AU - Jilma, Bernd
AU - Jüni, Peter
AU - Lawler, Patrick R.
AU - Marietta, Marco
AU - Marshall, John C.
AU - McArthur, Colin
AU - Miranda, Carlos Henrique
AU - Mirault, Tristan
AU - Morici, Nuccia
AU - Perepu, Usha
AU - Schörgenhofer, Christian
AU - Sholzberg, Michelle
AU - Spyropoulos, Alex C.
AU - Webb, Steve A.
AU - Zarychanski, Ryan
AU - Zuily, Stéphane
AU - Le Gal, Grégoire
AU - for the International Network of VENous Thromboembolism Clinical Research Networks INVENT-VTE
N1 - Funding Information: TT, LS, MR, TB, PMS, and SK are members; SM is the chair; and GLG the vice‐chair of INVENT‐VTE. TT, LS, MS, RZ, GLG are members and MR and SK are the co‐directors of the Canadian Venous Thromboembolism Research Network (CanVECTOR), which receives grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT‐142654). SM is the co‐chair of the Dutch Thrombosis Network. TB is a member of the Thrombosis and Haemostasis Society of Australasia and New Zealand (THANZ). PMS is a member of the Norwegian VECTOR Network. MM is a member of the Italian Society on Thrombosis and Haemostasis (SISET). TT is supported by a Fellowship Award from the CanVECTOR. MR is the McGill University Harry Webster Thorp Professor of Medicine. SK holds a Tier 1 Canada Research Chair in venous thromboembolism. PJ is a Tier 1 Canada Research Chair in Clinical Epidemiology of Chronic Diseases. GLG is supported by an Early Researcher Award from the Province of Ontario, a Mid‐Career Investigator Award from the Heart and Stroke Foundation of Ontario, and a Research Chair on the Diagnosis of Venous Thromboembolism, Department of Medicine, University of Ottawa. Funding Information: TT, LS, MR, TB, PMS, and SK are members; SM is the chair; and GLG the vice-chair of INVENT-VTE. TT, LS, MS, RZ, GLG are members and MR and SK are the co-directors of the Canadian Venous Thromboembolism Research Network (CanVECTOR), which receives grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT-142654). SM is the co-chair of the Dutch Thrombosis Network. TB is a member of the Thrombosis and Haemostasis Society of Australasia and New Zealand (THANZ). PMS is a member of the Norwegian VECTOR Network. MM is a member of the Italian Society on Thrombosis and Haemostasis (SISET). TT is supported by a Fellowship Award from the CanVECTOR. MR is the McGill University Harry Webster Thorp Professor of Medicine. SK holds a Tier 1 Canada Research Chair in venous thromboembolism. PJ is a Tier 1 Canada Research Chair in Clinical Epidemiology of Chronic Diseases. GLG is supported by an Early Researcher Award from the Province of Ontario, a Mid-Career Investigator Award from the Heart and Stroke Foundation of Ontario, and a Research Chair on the Diagnosis of Venous Thromboembolism, Department of Medicine, University of Ottawa. Funding Information: SM reports grants and fees paid to her institution, outside the present work, from Abbvie, BMS/Pfizer, Aspen, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Sanofi, and Portola. MC has funding from the US Department of Health and Human Services, National, Heart, Lung and Blood Diseases R01 HL141290. MC is a member of the Accelerating COVID‐19 Therapeutic Interventions and Vaccines (ACTIV)‐IV Steering Committee. MTD has participated in advisory boards from Apellis Pharmaceuticals, Bio Products Laboratory, and Sanofi Genzyme. BJ has provided scientific advice for Bayer, Guardian Therapeutics, Octapharma, and Sanofi. PJ serves as an unpaid member of steering group or executive committee of trials funded by Abbott Vascular, Astra Zeneca, Biotronik, Biosensors, St. Jude Medical, Terumo, and The Medicines Company; has received research grants to the institution from Appili Therapeutics, Astra Zeneca, Biotronik, Biosensors International, Eli Lilly, The Medicines Company; and honoraria to the institution for participation in advisory boards and/or consulting from Amgen, Ava, and Fresenius, but has not received personal payments by any pharmaceutical company or device manufacturer. MS is a member of the Accelerating COVID‐19 Therapeutic Interventions and Vaccines (ACTIV)‐IV Protocol Committee for the pre‐hospital outpatient population. ACS reports consultation fees from Bayer, Janssen, Boehringer Ingelheim, Portola, BMS, and the ATLAS group and research grants from Boehringer Ingelheim and Janssen. Remaining authors state that they have no conflicts of interest. RZ is the recipient of the Lyonel G. Israels Professorship in Hematology, University of Manitoba. RZ is a member of the Accelerating COVID‐19 Therapeutic Interventions and Vaccines (ACTIV)‐IV Steering Committee. The ACOVACT study is financially supported by the Austrian Federal Ministry of Education, Science and Research. The ATTACC trial is supported by the Canadian Institutes of Health Research, the Peter Munk Cardiac Centre, the LifeArc Foundation, and the Thistledown Foundation. Publisher Copyright: © 2020 International Society on Thrombosis and Haemostasis
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - anticoagulant
KW - COVID-19
KW - pulmonary embolism
KW - research networks
KW - thrombosis
UR - http://www.scopus.com/inward/record.url?scp=85091753303&partnerID=8YFLogxK
U2 - 10.1111/jth.15094
DO - 10.1111/jth.15094
M3 - Article
C2 - 32888372
AN - SCOPUS:85091753303
SN - 1538-7933
VL - 18
SP - 2958
EP - 2967
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 11
ER -