Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): Pilot/feasibility phase findings

For the Kids-Dott Trial Investigators

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1597-1605
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2015

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Random Allocation
Young Adult
Thrombosis
Randomized Controlled Trials
Venous Thromboembolism
Confidence Intervals
Safety
Antiphospholipid Antibodies
Feasibility Studies
Therapeutics
Venous Thrombosis
Anticoagulants
Blood Vessels
Pediatrics
Hemorrhage
Pilots

Keywords

  • Anticoagulants
  • Child
  • Clinical trial
  • Pilot study
  • Reliability and validity
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial) : Pilot/feasibility phase findings. / For the Kids-Dott Trial Investigators.

In: Journal of Thrombosis and Haemostasis, Vol. 13, No. 9, 01.09.2015, p. 1597-1605.

Research output: Contribution to journalArticle

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title = "Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): Pilot/feasibility phase findings",
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",
author = "{For the Kids-Dott Trial Investigators} and Goldenberg, {N. A.} and T. Abshire and Blatchford, {P. J.} and Fenton, {L. Z.} and Halperin, {J. L.} and Hiatt, {W. R.} and Kessler, {C. M.} and Kittelson, {J. M.} and Manco-Johnson, {M. J.} and Spyropoulos, {A. C.} and Steg, {P. G.} and Stence, {N. V.} and Turpie, {A. G G} and S. Schulman and R. Punzalan and M. Wang and J. Jaffray and G. Young and M. Rajpurkar and S. Carpenter and Y. Diab and N. Verdun and C. Tarango and S. Acharya and M. Torres and N. Kucine and B. Mitchell and N. Shah and C. Thornburg and C. Takemoto and R. Kulkarni and S. O'Brien and K. Haley and M. Recht and C. Knoll and C. Thornburg and A. Geddis and S. Ahuja and M. Simpson and L. Srivaths and J. Journeycake and A. Zia",
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T1 - Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial)

T2 - Pilot/feasibility phase findings

AU - For the Kids-Dott Trial Investigators

AU - Goldenberg, N. A.

AU - Abshire, T.

AU - Blatchford, P. J.

AU - Fenton, L. Z.

AU - Halperin, J. L.

AU - Hiatt, W. R.

AU - Kessler, C. M.

AU - Kittelson, J. M.

AU - Manco-Johnson, M. J.

AU - Spyropoulos, A. C.

AU - Steg, P. G.

AU - Stence, N. V.

AU - Turpie, A. G G

AU - Schulman, S.

AU - Punzalan, R.

AU - Wang, M.

AU - Jaffray, J.

AU - Young, G.

AU - Rajpurkar, M.

AU - Carpenter, S.

AU - Diab, Y.

AU - Verdun, N.

AU - Tarango, C.

AU - Acharya, S.

AU - Torres, M.

AU - Kucine, N.

AU - Mitchell, B.

AU - Shah, N.

AU - Thornburg, C.

AU - Takemoto, C.

AU - Kulkarni, R.

AU - O'Brien, S.

AU - Haley, K.

AU - Recht, M.

AU - Knoll, C.

AU - Thornburg, C.

AU - Geddis, A.

AU - Ahuja, S.

AU - Simpson, M.

AU - Srivaths, L.

AU - Journeycake, J.

AU - Zia, A.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

KW - Anticoagulants

KW - Child

KW - Clinical trial

KW - Pilot study

KW - Reliability and validity

KW - Thrombosis

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U2 - 10.1111/jth.13038

DO - 10.1111/jth.13038

M3 - Article

C2 - 26118944

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VL - 13

SP - 1597

EP - 1605

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

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