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.
authors.affiliation: All Children's Research Institute, All Children's Hospital Johns Hopkins Medicine, St Petersburg, FL, USA.|Departments of Pediatrics and Medicine, Divisions of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Goldenberg
authors.affiliation: Department of Pediatrics, Section of Hematology/Oncology/BMT, Medical College of Wisconsin, Milwaukee, WI, USA.|BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Abshire
authors.affiliation: Department of Biostatistics, School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Blatchford
authors.affiliation: Department of Pediatric Radiology, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: L Z
authors.initials: LZ
authors.lastname: Fenton
authors.affiliation: The Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Halperin
authors.affiliation: Department of Medicine, Division of Cardiology, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.|CPC Clinical Research, Aurora, CO, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Hiatt
authors.affiliation: Department of Medicine, Division of Hematology, Georgetown University School of Medicine, Washington, DC, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Kessler
authors.affiliation: Department of Biostatistics, School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Kittelson
authors.affiliation: 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.
authors.forename: M J
authors.initials: MJ
authors.lastname: Manco-Johnson
authors.affiliation: Department of Medicine, Division of Hematology, Hofstra North Shore - Long Island Jewish School of Medicine, Manhasset, NY, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Spyropoulos
authors.affiliation: Department of Cardiology, Département Hospitalo-Universitaire FIRE (Fibrosis-Inflammation-REmodelling), University Paris-Diderot, Paris, France.
authors.forename: P G
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Department of Biostatistics, School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: N V
authors.initials: NV
authors.lastname: Stence
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.|Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.
authors.forename: A G G
authors.initials: AG
authors.lastname: Turpie
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.|Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Schulman
mesh_terms: D000293:Adolescent; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003120:Colorado / Q000453:epidemiology; D003952:Diagnostic Imaging; D023381:Endpoint Determination / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005431:Florida / Q000453:epidemiology; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D015588:Observer Variation; D010865:Pilot Projects; D011785:Quality Assurance, Health Care; D012008:Recurrence; D015203:Reproducibility of Results; D012107:Research Design; D016037:Single-Blind Method; D013997:Time Factors; D020246:Venous Thrombosis / Q000175:diagnosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000925:Anticoagulants
keywords: anticoagulants; child; clinical trial; pilot study; reliability and validity; thrombosis