With advances in the care and invasive management of critically ill children, venous thromboembolism has become increasingly recognized in pediatrics over the past decade. Optimal treatment of thrombosis in children requires a skilled assessment of acute and long-term prothrombotic tendencies, risk of adverse post-thrombotic outpomes, and potential hemorrhagic complications. To date, the number of pediatric subspecialists who have gained expertise through formal mentored training in both the field of thrombosis/ thrombophilia and the discipline of clinical investigation is limited, and many of these individuals are senior in their careers. At the same time, few randomized controlled trials (RCTs) have provided clinical evidence for the management of thrombosis in children, and guidelines remain largely based upon adult data. Given these critical public health needs, the PRINCIPAL OBJECTIVE of this proposal is to provide the applicant with exceptional mentored training in pediatric thrombosis/thrombophilia and clinical/translational research, and to foster his mentored role in conducting a pilot/feasibility study for an original, web-based RCT (supported by, and performed via the network of, the Hemophilia and Thrombosis Research Society) that seeks to optimize the duration of anticoagulant therapy for venous thrombosis in children. The PRIMARY HYPOTHESIS of the study is that a shortened duration of anticoagulation is as effective, and at least as safe, as conventional-duration anticoagulation in children with acute venous thrombosis in whom early thrombus resolution has occurred and clinical and laboratory features constitute a low-risk for adverse post- thrombotic outcomes. Enrolled children will be treated acutely with anticoagulation according to the present standard of care;patients who demonstrate thrombus resolution radiologically at 6 weeks will then be randomized to undergo no further anticoagulation versus to complete a conventional 3-month course of therapy. Patients will be followed for 2 years with uniform assessment of bleeding complications, recurrent thromboembolism, and the post-thrombotic syndrome, for preliminary safety and efficacy comparison between the two regimens. Enrollment of 200 patients across 10 pilot sites will provide sufficient pilot data for, and demonstrate the feasibility of, the future definitive RCT. Additionally, translational studies will seek to identify novel candidate protein risk factors and prognostic markers for venous thrombosis in children.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL084055-04
Application #
7788826
Study Section
Special Emphasis Panel (ZHL1-CSR-R (F1))
Program Officer
Sarkar, Rita
Project Start
2007-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
4
Fiscal Year
2010
Total Cost
$148,521
Indirect Cost
Name
University of Colorado Denver
Department
Pediatrics
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Goldenberg, N A; Abshire, T; Blatchford, P J et al. (2015) Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): pilot/feasibility phase findings. J Thromb Haemost 13:1597-605
Amankwah, Ernest K; Atchison, Christie M; Arlikar, Shilpa et al. (2014) Risk factors for hospital-sssociated venous thromboembolism in the neonatal intensive care unit. Thromb Res 134:305-9
Atchison, Christie M; Arlikar, Shilpa; Amankwah, Ernest et al. (2014) Development of a new risk score for hospital-associated venous thromboembolism in noncritically ill children: findings from a large single-institutional case-control study. J Pediatr 165:793-8
Goldenberg, Neil A; Bernard, Timothy J; Hillhouse, Jasper et al. (2013) Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children. Haematologica 98:802-7
Goldenberg, Neil A; Jenkins, Sarah; Jack, Jessica et al. (2013) Arteriopathy, D-dimer, and risk of poor neurologic outcome in childhood-onset arterial ischemic stroke. J Pediatr 162:1041-6.e1
Lyle, Courtney A; Gibson, Elizabeth; Lovejoy, Amy E et al. (2013) Acute prognostic factors for post-thrombotic syndrome in children with limb DVT: a bi-institutional cohort study. Thromb Res 131:37-41
Pearson, Virginia; Ruzas, Chris; Krebs, Nancy F et al. (2013) Overweight and obesity are increased in childhood-onset cerebrovascular disease. J Child Neurol 28:517-9
Kittelson, J M; Spyropoulos, A C; Halperin, J L et al. (2013) Balancing risk and benefit in venous thromboembolism trials: concept for a bivariate endpoint trial design and analytic approach. J Thromb Haemost 11:1443-8
Bernard, Timothy J; Manco-Johnson, Marilyn J; Lo, Warren et al. (2012) Towards a consensus-based classification of childhood arterial ischemic stroke. Stroke 43:371-7
Branchford, Brian R; Mourani, Peter; Bajaj, Lalit et al. (2012) Risk factors for in-hospital venous thromboembolism in children: a case-control study employing diagnostic validation. Haematologica 97:509-15

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