Kids-DOTT: Prospective Multi-Center Evaluation of the Duration of Therapy for Thrombosis in Children (Protocol # 03-585)
The present proposal is for a definitive RCT powered to evaluate non-inferiority of shortened duration vs conventional duration anticoagulation in children with first episode acute venous thrombosis. There are 2 phases. Phase 1:Pilot/feasibility study to validate target sample size, after the first 200 subjects enrolled will be followed for 2 years for primary endpoint. Phase 2:completion of power trial. Subjects at the time of enrollement, children with acute venous thrombosis who meet eligibility criteria will have already undergone comprehensive thrombophilia testing and selection of anticoagulant provided by the primary clinician following the the standard of clinical practices. The drug will be provided and dispensed as a standard of care, with the exception of Dalteparin (IND 77926), which will be dispensed via the research pharmacy services. The dispensed and administration of Dalteparin will be considered a research procedure. Anticoagulant intensity will be monitor in accordance with the standard of care practices. At 6 weeks of anticoagulation therapy subjects with positive antiphopholipid antibody test will undergo repeat assessment of the previously positive test; children whose antiphospholipid antibody testing is still positive at that time will undergo exclusion from randomization in the trial, and instead continue to be followed in the study as a non-interventional, observational group. At 6 weeks of anticoagult therapy, all subjects will undergo a repeat of their original diagnostic imaging, using the same imaging used for the diagnosis of thrombosis by the site.
All subjects will undergo follow up assessments at 3, 6, 12, [AND]amp; yearly through 5 years post-diagnosis within standard clinical care practices for pediatric venous thrombosis. Phone interviews will be conducted at 2, 4, [AND]amp; 5 months to establish symptoms of possible concern for recurrent VTE.
The prospective information collected for analysis will be collected from the medical records, these include suspicion of recurrent VTE and imagine findigs. Radiologist and PTS examiners will be blinded to the treatment allocation. The coordinating center will also review the imaging studies to evaluate accuracy.
Target of pilot study is 200. For the entire trial a estimation of 750 among the centers. Enrollment target will have been achieved when 892 randomized subjects reach the 2-year follow-up endpoint.
The study also looks to establish a clinical trial-derived plasma and nucleic acids biorepository for future proteomic, genomic, and metabolomic investigations of predictors and modulators of VTE outcomes in children.
(1) Children (birth to <21 years of age) with radiologically-confirmed acute venous thrombosisin the past 30 days
(2) In the opinion of the investigator, the venous thrombosis was a provoked (i.e., non-spontaneous) event (e.g.: hospitalization; Central venous catheterization; infection; dehydration; surgery; trauma; immobility; use of estrogen-containing oral contraceptive pills; flare of autoimmune/rheumatologic condition).