Randomized Controlled Trial

. 2025 Feb;23(2):651-656.

doi: 10.1016/j.jtha.2024.09.038. Epub 2024 Oct 24.

Duration of anticoagulation for venous thromboembolism in pediatric patients: Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) trial outcomes at 2 years

Neil A Goldenberg¹, Sam Schulman², John M Kittelson³, Thomas C Abshire⁴, James F Casella⁵, Rita Dale⁶, Jonathan L Halperin⁷, Jade Hanson⁸, Craig M Kessler⁹, Marilyn J Manco-Johnson¹⁰, Laurel McDevitt⁸, Robert F Sidonio¹¹, Alex C Spyropoulos¹², P Gabriel Steg¹³, Marc P Bonaca¹⁴; Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) Trial Investigators and the Antithrombotic Trials Leadership and Steering (ATLAS) Group

Collaborators, Affiliations

Collaborators

Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) Trial Investigators and the Antithrombotic Trials Leadership and Steering (ATLAS) Group:
S Acharya, S Ahuja, M Betensky, R Bhat, M Bhatt, A Borst, L Brandao, S Carpenter, A Bruce, A Chan, J Cooper, F Corrales-Medina, S Cramer, S Crary, S Dandekar, J Davila, Y Diab, C Druzgal, J Fargo, K Haley, K Hege, J Jaffray, O Khan, C Knoll, N Kucine, R Kulkarni, R Kumar, C Lawrence, C Lo, E Lowe, A Mahajerin, C Male, P Massicotte, R Mignacca, D Mitchell, P Monagle, C Mullen, C Nakar, S Narang, S O'Brien, A Panigrahi, M Rajpurkar, D Raybagkar, A Scott-Emuakpor, N Shah, A Sharathkumar, L Srivaths, C Thornburg, C Takemoto, C Tarango, M Torres, H van Ommen, A Verma, M Wang, H Wilson, G Woods, F Xavier, G Young, A Zia, M Bonaca, N Cutler, C Kessler, N Goldenberg, J Halperin, S Schulman, A Spyropoulos, P Steg, J Weitz

Affiliations

¹ Johns Hopkins All Children's Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address: neil@jhmi.edu.
² Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Cardiology, Obstetrics and Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
³ Department of Biostatistics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; CPC Clinical Research, Aurora, Colorado, USA.
⁴ Department of Pediatrics and Medicine, Clinical & Translational Science Institute, Versiti Blood Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁵ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁶ Department of Biostatistics, Worldwide Clinical Trials, Research Triangle Park, North Carolina, USA.
⁷ The Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁸ Johns Hopkins All Children's Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.
⁹ Department of Medicine, Georgetown University School of Medicine, Lombardi Comprehensive Cancer Center, Washington, D.C., USA.
¹⁰ Department of Pediatrics, School of Medicine, Children's Hospital of Colorado, Hemophilia and Thrombosis Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹¹ Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
¹² Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Feinstein Institutes for Medical Research, Manhasset, New York, USA.
¹³ Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, French Alliance for Cardiovascular Trials, Institut National de la Santé et de la Recherche Médicale 1148, Université Paris-Cité, Paris, France.
¹⁴ CPC Clinical Research, Aurora, Colorado, USA; Division of Cardiology, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA.

PMID: 39461724
PMCID: PMC11786982 (available on 2026-02-01)
DOI: 10.1016/j.jtha.2024.09.038

Randomized Controlled Trial

Duration of anticoagulation for venous thromboembolism in pediatric patients: Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) trial outcomes at 2 years

Neil A Goldenberg et al. J Thromb Haemost. 2025 Feb.

. 2025 Feb;23(2):651-656.

doi: 10.1016/j.jtha.2024.09.038. Epub 2024 Oct 24.

Authors

Collaborators

Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) Trial Investigators and the Antithrombotic Trials Leadership and Steering (ATLAS) Group:
S Acharya, S Ahuja, M Betensky, R Bhat, M Bhatt, A Borst, L Brandao, S Carpenter, A Bruce, A Chan, J Cooper, F Corrales-Medina, S Cramer, S Crary, S Dandekar, J Davila, Y Diab, C Druzgal, J Fargo, K Haley, K Hege, J Jaffray, O Khan, C Knoll, N Kucine, R Kulkarni, R Kumar, C Lawrence, C Lo, E Lowe, A Mahajerin, C Male, P Massicotte, R Mignacca, D Mitchell, P Monagle, C Mullen, C Nakar, S Narang, S O'Brien, A Panigrahi, M Rajpurkar, D Raybagkar, A Scott-Emuakpor, N Shah, A Sharathkumar, L Srivaths, C Thornburg, C Takemoto, C Tarango, M Torres, H van Ommen, A Verma, M Wang, H Wilson, G Woods, F Xavier, G Young, A Zia, M Bonaca, N Cutler, C Kessler, N Goldenberg, J Halperin, S Schulman, A Spyropoulos, P Steg, J Weitz

Affiliations

¹ Johns Hopkins All Children's Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address: neil@jhmi.edu.
² Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Cardiology, Obstetrics and Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
³ Department of Biostatistics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; CPC Clinical Research, Aurora, Colorado, USA.
⁴ Department of Pediatrics and Medicine, Clinical & Translational Science Institute, Versiti Blood Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁵ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁶ Department of Biostatistics, Worldwide Clinical Trials, Research Triangle Park, North Carolina, USA.
⁷ The Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁸ Johns Hopkins All Children's Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.
⁹ Department of Medicine, Georgetown University School of Medicine, Lombardi Comprehensive Cancer Center, Washington, D.C., USA.
¹⁰ Department of Pediatrics, School of Medicine, Children's Hospital of Colorado, Hemophilia and Thrombosis Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹¹ Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
¹² Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Feinstein Institutes for Medical Research, Manhasset, New York, USA.
¹³ Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, French Alliance for Cardiovascular Trials, Institut National de la Santé et de la Recherche Médicale 1148, Université Paris-Cité, Paris, France.
¹⁴ CPC Clinical Research, Aurora, Colorado, USA; Division of Cardiology, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA.

PMID: 39461724
PMCID: PMC11786982 (available on 2026-02-01)
DOI: 10.1016/j.jtha.2024.09.038

Abstract

Background: The Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children multinational, randomized clinical trial revealed noninferiority of a 6-week vs 3-month duration of anticoagulation for the treatment of provoked venous thromboembolism (VTE) in patients <21 years old in regard to net clinical benefit at 1 year.

Objectives: To evaluate noninferiority at 2 years.

Methods: Patients whose repeat imaging 6 weeks after VTE diagnosis did not show complete veno-occlusion were randomized to discontinue anticoagulation vs receive a total 3-month course and followed for 2 years for the occurrence of symptomatic recurrent VTE (efficacy outcome) and clinically relevant bleeding (safety outcome). Outcomes were centrally adjudicated, and net clinical benefit was compared between treatment arms via a prespecified bivariate noninferiority boundary, using 95% CIs in absolute risk differences between treatment arms.

Results: Kaplan-Meier estimates of 2-year cumulative incidences in the 6-week and 3-month arms of the intention-to-treat population (n = 417) were 1.7% (95% CI, 0%, 3.7%) and 2.9% (95% CI, 0.3%, 5.4%), respectively, for symptomatic recurrent VTE and 1.1% (95% CI, 0%, 2.5%) and 3.2% (95% CI, 0.6%, 5.7%), respectively, for clinically relevant bleeding. Bivariate analysis of the absolute risk differences in the intention-to-treat population demonstrated that a 6-week anticoagulation duration was noninferior to a 3-month course.

Conclusion: These findings support durability of the Kids-DOTT randomized clinical trial findings of net clinical benefit at 2 years.

Keywords: anticoagulation; children; duration; treatment; venous thromboembolism.

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Conflict of interest statement

Declaration of Competing Interests N.A.G.: consulting fees and/or honoraria from Anthos Therapeutics, Bayer, Johnson & Johnson, Novartis, and the University of Colorado-affiliated Academic Research Organization CPC Clinical Research for roles in clinical trial planning or oversight committees (eg, advisory, steering, and data and safety monitoring committees). S.S.: honoraria from Bayer Healthcare, Boehringer Ingelheim, Hemostasis Reference Laboratory, Regeneron, Sanofi, and Takeda. J.M.K.: none. T.C.A.: none. J.F.C.: none. R.D.: none. J.L.H.: honoraria from Abbott, Anthos Therapeutics, and Bayer Healthcare for membership in oversight committees (Executive Steering or Independent Data Monitoring). J.H.: none. C.M.K.: research support from Bayer, Genentech, Octapharma, Novo Nordisk, and Stago. Consulting fees from Bayer, CSL, Genentech, Novo Nordisk, Novartis, Octapharma, Stago, and Takeda. Honoraria from Bayer and Octapharma for membership in Data and Safety Monitoring Committees. M.J.M.-J.: honoraria from BioMarin, CSL Behring, Genentech, and Pfizer. L.M.: none. R.F.S.: research support from Takeda, Octapharma, and LFB related to inherited bleeding disorders. Honoraria from Takeda, Octapharma, LFB, Sanofi/Sobi, Genentech/Roche, Bayer, Pfizer, Guardian Therapeutics, Vega, Novo Nordisk, and HEMAb. A.C.S.: consulting fees from Alexion, AstraZeneca, Bristol Myers Squibb, Janssen, Medscape Cardiology, Roche, Regeneron, and Sanofi. Salary support from the Broxmeyer Fellowship in Clinical Thrombosis. P.G.S.: compensated officer (Chief Medical Officer), Bioquantis (artificial intelligence diagnostics company). Research support from Amarin, AstraZeneca, and Sanofi. Consulting fees from Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Idorsia, Novartis, Novo Nordisk, PhaseBio, Pfizer, and Sanofi. M.P.B.: consulting fees and/or research support from Abbott Laboratories, Agios Pharmaceuticals, Inc, Alexion Pharma, Alnylam Pharmaceuticals, Inc, Amgen Inc, Angionetics, Inc, Anthos Therapeutics, ARCA Biopharma, Inc, Array BioPharma, Inc, AstraZeneca and Affiliates, Atentiv LLC, Audentes Therapeutics, Inc, Bayer and Affiliates, Beth Israel Deaconess Medical Center, Better Therapeutics, Inc, Boston Clinical Research Institute, Bristol Meyers Squibb Company, Cambrian Biopharma, Inc, Cardiol Therapeutics Inc, CellResearch Corp, Cleerly Inc, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc, EP Trading Co, Ltd, EPG Communication Holdings Ltd, Epizon Pharma, Inc, Esperion Therapeutics, Inc, Everly Well, Inc, Exicon Consulting Pvt. Ltd, Faraday Pharmaceuticals, Inc, Foresee Pharmaceuticals Co, Ltd, Fortress Biotech, Inc, HDL Therapeutics Inc, HeartFlow Inc, Hummingbird Bioscience, Insmed Inc, Ionis Pharmaceuticals, IQVIA Inc, Janssen and Affiliates, Kowa Research Institute, Inc, Kyushu University, Lexicon Pharmaceuticals, Inc, Medimmune Ltd, Medpace, Merck & Affiliates, Nectero Medical Inc, Novartis Pharmaceuticals Corp, Novo Nordisk, Inc, Osiris Therapeutics Inc, Pfizer Inc, PhaseBio Pharmaceuticals, Inc, PPD Development, LP, Prairie Education and Research Cooperative, Prothena Biosciences Limited, Regeneron Pharmaceuticals, Inc, Regio Biosciences, Inc, Saint Luke’s Hospital of Kansas City, Sanifit Therapeutics S.A., Sanofi-Aventis Groupe, Silence Therapeutics PLC, Silence, Smith & Nephew plc, Stanford Center for Clinical Research, Stealth BioTherapeutics Inc, The Brigham & Women’s Hospital, Inc, The Feinstein Institutes for Medical Research, Thrombosis Research Institute, University of Colorado, University of Pittsburgh, VarmX, Virta Health Corporation, Worldwide Clinical Trials Inc, WraSer, LLC, and Yale Cardiovascular Research Group. Salary support and research support via grants from the American Heart Association (18SFRN3390085 and 18SFRN33960262) and the State of Colorado.

References

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Duration of anticoagulation for venous thromboembolism in pediatric patients: Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) trial outcomes at 2 years

Collaborators

Affiliations

Duration of anticoagulation for venous thromboembolism in pediatric patients: Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) trial outcomes at 2 years

Authors

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Abstract

Conflict of interest statement

References

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