1. Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): pilot/feasibility phase findings.
- Author
-
Goldenberg NA, Abshire T, Blatchford PJ, Fenton LZ, Halperin JL, Hiatt WR, Kessler CM, Kittelson JM, Manco-Johnson MJ, Spyropoulos AC, Steg PG, Stence NV, Turpie AG, and Schulman S
- Subjects
- Adolescent, Anticoagulants administration & dosage, Anticoagulants adverse effects, Child, Child, Preschool, Colorado epidemiology, Diagnostic Imaging, Endpoint Determination methods, Feasibility Studies, Female, Florida epidemiology, Hemorrhage chemically induced, Hemorrhage epidemiology, Humans, Infant, Male, Observer Variation, Pilot Projects, Quality Assurance, Health Care, Recurrence, Reproducibility of Results, Research Design, Single-Blind Method, Time Factors, Venous Thrombosis diagnosis, Young Adult, Anticoagulants therapeutic use, Venous Thrombosis drug therapy
- Abstract
Background: Randomized controlled trials (RCTs) on pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success., Methods: The Kids-DOTT trial is a multicenter RCT investigating non-inferiority of a 6-week (shortened) versus 3-month (conventional) duration of anticoagulation in patients aged < 21 years with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded-endpoint, parallel-cohort RCT design., Results: No eligibility violations or randomization errors occurred. Of the enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in prespecified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Interobserver agreement between local and blinded central determination of venous occlusion by imaging at 6 weeks after diagnosis was strong (k-statistic = 0.75; 95% confidence interval [CI] 0.48-1.0). The primary efficacy and safety event rates were 3.3% (95% CI 0.3-11.5%) and 1.4% (95% CI 0.03-7.4%)., Conclusions: The P/F phase of the Kids-DOTT trial has demonstrated the validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention and endpoint rates to inform the fully powered RCT., (© 2015 International Society on Thrombosis and Haemostasis.)
- Published
- 2015
- Full Text
- View/download PDF