Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): pilot/feasibility phase findings
N A Goldenberg, T Abshire, P J Blatchford, L Z Fenton, J L Halperin, W R Hiatt, C M Kessler, J M Kittelson, M J Manco-Johnson, A C Spyropoulos, P G Steg, N V Stence, A G G Turpie, S Schulman, Kids-DOTT Trial Investigators, N Goldenberg, R Punzalan, M Wang, J Jaffray, G Young, M Rajpurkar, S Carpenter, Y Diab, N Verdun, C Tarango, S Acharya, M Torres, N Kucine, B Mitchell, N Shah, C Thornburg, C Takemoto, R Kulkarni, S O'Brien, K Haley, M Recht, C Knoll, C Thornburg, A Geddis, S Ahuja, M Simpson, L Srivaths, J Journeycake, A Zia, N A Goldenberg, T Abshire, P J Blatchford, L Z Fenton, J L Halperin, W R Hiatt, C M Kessler, J M Kittelson, M J Manco-Johnson, A C Spyropoulos, P G Steg, N V Stence, A G G Turpie, S Schulman, Kids-DOTT Trial Investigators, N Goldenberg, R Punzalan, M Wang, J Jaffray, G Young, M Rajpurkar, S Carpenter, Y Diab, N Verdun, C Tarango, S Acharya, M Torres, N Kucine, B Mitchell, N Shah, C Thornburg, C Takemoto, R Kulkarni, S O'Brien, K Haley, M Recht, C Knoll, C Thornburg, A Geddis, S Ahuja, M Simpson, L Srivaths, J Journeycake, A Zia
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.
Keywords: anticoagulants; child; clinical trial; pilot study; reliability and validity; thrombosis.
© 2015 International Society on Thrombosis and Haemostasis.
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Source: PubMed