Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT)

This study is currently recruiting participants.
Verified January 2013 by University of Colorado, Denver
Sponsor:
Collaborators:
Hemophilia and Thrombosis Research Society
Eisai Inc.
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00687882
First received: May 6, 2008
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

The Kids-DOTT trial is a randomized controlled clinical trial whose primary objective is to evaluate non-inferiority of shortened-duration (6 weeks) versus conventional-duration (3 months) anticoagulation in children with first-episode acute venous thrombosis. The first stage of the trial has consisted of a pilot/feasibility component, which then continues as the definitively-powered trial.


Condition Intervention Phase
Venous Thrombosis
Other: Shortened duration (6 weeks) of anticoagulant therapy
Other: Conventional duration (3 months) of anticoagulant therapy
Other: No Intervention
Drug: Dalteparin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective Multi-Center Evaluation of the Duration of Therapy for Thrombosis in Children

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Bivariate endpoint. [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

    Primary efficacy endpoint is the risk of symptomatic, radiologically-confirmed recurrent venous thromboembolism.

    Primary safety endpoint is clinically-relevant bleeding (major + clinically-relevant non-major).



Secondary Outcome Measures:
  • Prevalence/severity of post-thrombotic syndrome. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    PTS is measured using a standardized validated pediatric outcome instrument (Manco-Johnson instrument). Both PTS and clinically-significant PTS will be captured as secondary endpoints.


Estimated Enrollment: 750
Study Start Date: March 2008
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Intervention: A
Patients with non-occlusive thrombus or resolved thrombosis at 6 weeks.
Other: Shortened duration (6 weeks) of anticoagulant therapy
Subjects with evidence of non-occlusive or resolved thrombus at 6 weeks time will be randomized to receive a total duration of anticoagulant therapy of 6 weeks.
Active Comparator: B
Patients with non-occlusive thrombus or resolved thrombosis at 6 weeks.
Other: Conventional duration (3 months) of anticoagulant therapy
Subjects with evidence of non-occlusive or resolved thrombus at 6 weeks time will be randomized to receive a total duration of anticoagulant therapy of 3 months.
Parallel Cohort: Persistent Occlusive Thrombosis
Patients with completely occlusive thrombosis at 6 weeks.
Other: No Intervention
Subjects with evidence of persistent thrombus at 6 weeks time will remain on anticoagulant therapy for 3-6 months at the discretion of their treating physician.
Parallel Cohort: Persistent Antiphospholipid Antibody
Patients with persistent Positive Antiphospholipid Antibody at 6 weeks.
Other: No Intervention
Subjects with evidence of persistent antiphospholipid antibody at 6 weeks will remain on anticoagulant therapy for 3 months to indefinite duration, at the discretion of their treating physician.
Interventional: Dalteparin Substudy
Use of investigational dalteparin in lieu of formulary low molecular weight heparin in those children who are clinically prescribed a low molecular weight heparin for sub-acute anticoagulation.
Drug: Dalteparin
Other Name: Fragmin®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children, aged 0- <21 years at time of enrollment
  • Recently-diagnosed (i.e., within 30 days of radiologic diagnosis) of first- episode acute venous thrombosis

Exclusion Criteria:

  • 1) Any one of the following:

    1. history of premature birth, if corrected (i.e., post-conceptional) age < 36 weeks (including gestation) at time of enrollment;
    2. pregnancy at time of enrollment (N.B.: development of pregnancy while on study will constitute post-enrollment exclusion from the study, although any data collected to that time will be retained given the intent-to-treat analytic approach);
    3. known pulmonary embolism complicating this first-episode venous thrombosis;
    4. uncorrected anatomic vascular defect, including May-Thurner anomaly, cervical rib, and atretic IVC;
    5. use of thrombolytic therapy (i.e. tPA) in the treatment of this first-episode venous thrombosis;
    6. chronic inflammatory condition/disease, other than diabetes mellitus;
    7. prior episode of treated VTE;
    8. antiphospholipid antibody persistent at 6 weeks (anticardiolipin IgM ≥ 20, anti-beta-2-glycoprotein-1 IgG or IgM ≥ 10, or lupus anticoagulant positive by local laboratory parameters, e.g. LA1/LA2 ratio ≥ 1.2 by dRVVT);
    9. combined elevation of factor VIII > 150 IU/dL and D-dimer > 500 ng/mL at diagnosis in patients with veno-occlusive DVT involving the extremities, iliac veins, IVC, subclavian vein, brachiocephalic vein, innominate vein, or SVC;
    10. history of malignancy;
    11. no identifiable clinical risk factor for thrombosis (i.e., episode is spontaneous);
    12. homozygous factor V Leiden mutation;
    13. homozygous prothrombin 20210 mutation;
    14. protein C below lower limit of normal values for age (local laboratory, if patient is < 3 months of age) or protein C less than 40% (IU/dL)if the patient is ≥ 3 months of age;
    15. protein S below 40% (IU/dL);
    16. antithrombin below lower limit of normal values for age (local laboratory, if patient is < 3 months of age) or antithrombin less than 60 % (IU/dL) if the patient is 3 months of age or older at time of enrollment for patients who will be treated with dalteparin (FRAGMIN®);
    17. Two or more separate, non-contiguous thrombi simultaneously;
    18. Systemic lupus erythematosus (SLE);
    19. DALTEPARIN SUBSTUDY ONLY: estimated creatinine clearance <60ml/min. or the patient weighs 8 kg at the time of enrollment.

      • OR
  • 2) At least three of the following:

    1. first-degree family history of VTE (full sibling or biological parent treated for VTE before 50 years of age);
    2. thrombophilia traits at most recent assessment prior to enrollment as follows (each counted individually as one risk factor):

      1. factor V Leiden mutation;
      2. prothrombin 20210 mutation;
      3. protein C below lower limit of normal values for age (local laboratory, if patient is < 3 months of age), or protein C less than 40% (IU/dL) if patient is ≥ 3 months);
      4. protein S below 40%;
      5. antithrombin below lower limit of normal values for age (local laboratory, if patient is < 3 months of age) or antithrombin less than 60% (IU/dL) if patient is ≥ 3 months);
      6. homocysteine ≥ 14 microM;
      7. antiphospholipid antibody positive at enrollment; (anticardiolipin IgM ≥ 20); GPL/MPL, anti-beta-2- glycoprotein-1 IgG or IgM ≥ 10 GPL/MPL, or lupus anticoagulant positive by local laboratory parameters,e.g.LA1/LA2 ration ≥ 1.2 by dRVVT).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00687882

Contacts
Contact: Neil A Goldenberg, MD 727-767-6886 neil.goldenberg@allkids.org
Contact: Amy E Wallace, MA 720-777-4710 amy.wallace@childrenscolorado.org

Locations
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Contact: Holly Davidson    602-546-0171    hdavidson@phoenixchildrens.com   
Principal Investigator: Christine Knoll, MD         
United States, California
Rady Children's Hospital UCSD Recruiting
San Diego, California, United States, 92123
Contact: Theresa Vella    858-966-1700 ext 7376    tvella@rchsd.org   
Principal Investigator: Amy Geddis, MD         
United States, Colorado
University of Colorado School of Medicine Recruiting
Denver, Colorado, United States, 80045
Contact: Michael Wang, MD    303-724-3492    michael.wang@ucdenver.edu   
Contact: Julie Smith, BA    303-724-6187    julie.smith@ucdenver.edu   
Principal Investigator: Michael Wang, MD         
United States, District of Columbia
George Washington University, Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Juan Carlos Arroyo    202-476-5385    JCArroyo@cnmc.org   
Contact: Amanda Kasper, MPH    (202) 476-2753    akasper@childrensnational.org   
Principal Investigator: Yaser Diab, M.D.         
United States, Florida
All Children's Hospital Recruiting
St. Petersburg, Florida, United States, 33701
Contact: Frances Hamblin    727-767-2423    Frances.Hamblin@allkids.org   
Principal Investigator: Neil Goldenberg, MD         
United States, Michigan
Children's Hospital of Michigan, Wayne State University Recruiting
Detroit, Michigan, United States, 48201
Contact: Kristy Enderlan    313-966-8393    kenderle@dmc.org   
Principal Investigator: Madhvi Rajpurkar, MD         
Michigan State University Recruiting
East Lansing, Michigan, United States, 48824
Contact: Sue Adkins    517-432-5126    Sue.Adkins@hc.msu.edu   
Principal Investigator: Roshni Kulkarni, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Hai Huang    919-613-4676    h.hai@duke.edu   
Principal Investigator: Courtney Thornburg, M.D.         
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Dianna Hidalgo    614-722-6885    disnna.hidalgo@nationwidechildrens.org   
Principal Investigator: Sarah O'Brien, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Anna Bican    615-875-3333    anna.bican@vanderbilt.edu   
Principal Investigator: Jennifer Domm, MD         
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Anna Winborn    214-456-8185    Anna.Winborn@childrens.com   
Principal Investigator: Janna Journeycake, MD         
Cook Children's Hospital Recruiting
Fort Worth, Texas, United States, 76104
Contact: Patricia Burns    682-885-7609    Patricia.Burns@cookchildrens.org   
Contact: Melinda Meacham, R.N., M.S.N.    682.885.    Melinda.Meacham@cookchildrens.org   
Principal Investigator: Marcela Torres, M.D.         
Texas Children's Cancer Center, Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Rosa Cole    832-824-4230    rxcole@txccc.org   
Contact: Margaret Nagel    832-824-1538    menagel@txch.org   
Principal Investigator: Lakshmi Venkateswaran, M.D.         
United States, Wisconsin
Medical College of Wisconsin, Blood Center of Wisconsin Recruiting
Wauwatosa, Wisconsin, United States, 53226
Contact: Megan Lemanczyk    414-937-6583    Megan.Lemanczyk@bcw.edu   
Principal Investigator: Rowena Punzalan, M.D.         
Sponsors and Collaborators
University of Colorado, Denver
Hemophilia and Thrombosis Research Society
Eisai Inc.
Investigators
Principal Investigator: Neil A Goldenberg, MD, PhD University of Colorado Denver Health Sciences Center
  More Information

Additional Information:
No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00687882     History of Changes
Other Study ID Numbers: 03-0585
Study First Received: May 6, 2008
Last Updated: January 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Venous Thromboembolism
Postthrombotic Syndrome
Antithrombotic Therapy
Duration of Therapy
Children

Additional relevant MeSH terms:
Thrombosis
Venous Thrombosis
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thromboembolism
Anticoagulants
Heparin, Low-Molecular-Weight
Dalteparin
Antibodies, Antiphospholipid
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014