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J Thromb Haemost. 2015 Sep;13(9):1597-605. doi: 10.1111/jth.13038. Epub 2015 Aug 11.

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

Author information

1
All Children's Research Institute, All Children's Hospital Johns Hopkins Medicine, St Petersburg, FL, USA.
2
Departments of Pediatrics and Medicine, Divisions of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
Department of Pediatrics, Section of Hematology/Oncology/BMT, Medical College of Wisconsin, Milwaukee, WI, USA.
4
BloodCenter of Wisconsin, Milwaukee, WI, USA.
5
Department of Biostatistics, School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
6
Department of Pediatric Radiology, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
7
The Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
8
Department of Medicine, Division of Cardiology, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
9
CPC Clinical Research, Aurora, CO, USA.
10
Department of Medicine, Division of Hematology, Georgetown University School of Medicine, Washington, DC, USA.
11
Department of Pediatrics, Section of Hematology/Oncology/BMT, and Hemophilia and Thrombosis Center, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
12
Department of Medicine, Division of Hematology, Hofstra North Shore - Long Island Jewish School of Medicine, Manhasset, NY, USA.
13
Department of Cardiology, Département Hospitalo-Universitaire FIRE (Fibrosis-Inflammation-REmodelling), University Paris-Diderot, Paris, France.
14
Department of Medicine, McMaster University, Hamilton, ON, Canada.
15
Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.

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

PMID:
26118944
PMCID:
PMC4561031
DOI:
10.1111/jth.13038
[Indexed for MEDLINE]
Free PMC Article

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