KidsDOTT-CCC

摘要

ABSTRACT The incidence of venous thromboembolism (VTE) has dramatically increased in children in recent years, to 1 in 200 hospitalized children. Annual health care costs can be estimated at $72M in the U.S. alone. Current international recommendations for duration of anticoagulant therapy in pediatric VTE are based upon findings of randomized controlled trials (RCTs) in adults, but call for devoted pediatric trials. The PRINCIPAL OBJECTIVE of this proposal is to conduct a definitive multicenter RCT to establish the duration of anticoagulation for venous thrombosis in children (the Kids-DOTI trial). The Clinical Coordinating Center is one of the nation's leading academic medical and research centers, Johns Hopkins University, and is led by the Chief Research Officer and Pediatric Thrombosis Program Director of its stand-alone pediatric tertiary care hospital, All Children's Hospital Johns Hopkins Medicine. The Data Coordinating Center is the University of Colorado and its affiliated non-profit Academic Research Organization CPC Clinical Research, which has extensive DCC experience and independent committee management in vascular disease trials. The PRIMARY HYPOTHESIS of Kids-DOTT is that, in children with a first episode of provoked acute venous thrombosis, a shortened duration of anticoagulation (6 weeks) is just as effective, and at least as safe (i.e., "non-inferior"), to conventional-duration therapy (3 months). The primary efficacy and safety endpoints are symptomatic recurrent VTE and anticoagulant­ associated, clinically-relevant bleeding, adjudicated by a blinded Clinical Endpoint Adjudication Committee. The trial is overseen by a Steering Committee and a Data and Safety Monitoring Committee. The research takes advantage of international pediatric guidelines for uniform dosing and monitoring of anticoagulants administered in routine clinical care, and tests for any subgroup effects of specific anticoagulant drugs in a secondary aim. As an additional aim, a trial biorepository of plasma and genetic material will be established to faciliate future research on prognostic markers in well-characterized children with venous thrombosis. The pilot/feasibility phase of the trial was initiated under an NHLBI K23 and recently completed (target sample size, 100 patients enrolled on a multicenter basis), which has validated assumptions regarding recruitment and retention, shown high inter-rater reliability of radiologic criteria for randomization, demonstrated a very low rate of major protocol deviations, and provided key estimates on endpoint rates.