Evaluation of the Duration of Therapy for Thrombosis in Children
NCT ID: NCT00687882
Last Updated: 2025-06-18
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
532 participants
INTERVENTIONAL
2008-03-31
2022-02-15
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Collaborative Risk-stratified Investigation in Teen Inpatients With Critical Illness: Anticoagulation With LMWH in Kids for ThromboProphylaxis (CRITICAL-Kids-TP)
NCT06628778
Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial
NCT02767232
Safety of Dabigatran Etexilate in Blood Clot Prevention in Children
NCT02197416
Pharmacokinetics, Safety and Tolerability of Dabigatran Etexilate Solution in Children 1 to < 2 Years of Age
NCT01773174
Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Trial
NCT03003390
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Patients with residual occlusive thrombosis or persistent APA are excluded from randomization, and followed on parallel cohort arms (observational), with conventional anticoagulation durations. All other patients are randomized to a total anticoagulant duration of 6 weeks versus 3 months. Children are followed for primary efficacy endpoints of symptomatic recurrent venous thromboembolism (VTE) and primary safety endpoints of clinically-relevant bleeding (major plus clinically-relevant non-major, as per International Society of Thrombosis and Haemostasis Scientific and Standardization Committee \[Journal of Thrombosis \& Haemostasis\] 2012 definitions/recommendations).
Children are followed through 2 years (with primary endpoint at 1 year). Those with deep venous thromboses affecting venous return from the limbs also undergo standardized post-thrombotic syndrome (PTS) outcome assessment using the Manco-Johnson pediatric PTS instrument.
The non-inferiority analysis uses a bivariate endpoint approach, modeling the inherent clinical trade-off between the risks of recurrent VTE and bleeding. The trial will enroll 750 children across 40 participating centers, and allows for a 25% rate of exclusion from the per-protocol population due to randomization non-eligibility (i.e. parallel cohort), withdrawal/loss to follow-up, and protocol non-adherence.
A sub-study, completed in late 2013, used investigational dalteparin in lieu of formulary low molecular weight heparin (typically enoxaparin) in those children who were clinically prescribed a low molecular weight heparin for sub-acute anticoagulation. The goal of this sub-study was to report dose-finding and outcomes data in children treated with dalteparin for VTE. Outcomes in these patients were qualitatively compared with those of patients who received enoxaparin, warfarin, or other anticoagulants for sub-acute anticoagulation. This portion of the study was an industry-sponsored investigator-initiated sub-study with an investigator-held IND. Since the closure of the sub-study, the overall Kids-DOTT study is no longer conducted under an Investigational New Drug (IND) application.
Principal aims and hypotheses:
Specific Aim #1: To evaluate the efficacy and safety of shortened-duration (6 weeks total) versus conventional-duration (3 months total) anticoagulation for first-episode, provoked, acute venous thrombosis among children in whom thrombus resolution/non-occlusion (i.e. established blood flow) is evident after the initial 6 weeks of anticoagulant therapy
Hypothesis: Among children with first-episode, provoked, acute venous thrombosis in whom thrombosis is resolved or non-occlusive at six weeks follow-up, a shortened duration of anticoagulation (total six weeks; i.e. no further therapy) is non-inferior in efficacy to the conventional duration (total three months) of anticoagulation with respect to the risk of symptomatic recurrent VTE at 1 year, and is superior in safety with respect to the risk of clinically-relevant bleeding.(The hypothesis will also be tested in secondary analysis at 2 years, using the same efficacy and safety outcomes as for the 1 year primary analysis.)
Specific Aim #2: To compare the composite efficacy of shortened-duration (6 weeks total) versus conventional-duration (3 months total) anticoagulation for first-episode, provoked, acute venous thrombosis among children in whom thrombus resolution/non-occlusion (i.e., blood flow) is evident after the initial 6 weeks of anticoagulant therapy.
Hypothesis: Among children with first-episode, provoked, acute venous thrombosis in whom thrombosis is resolved or non-occlusive at six weeks follow-up, a shortened duration of anticoagulation (total six weeks; i.e. no further therapy) is non-inferior to the conventional duration (total three months) of anticoagulation with respect to a composite efficacy endpoint comprised of the 1-year risk of symptomatic recurrent VTE or PTS. (The hypothesis will also be tested in secondary analysis at 2 years.)
Specific Aim #3: To determine whether outcomes of first-episode, provoked, acute venous thrombosis (specifically, with respect to recurrent VTE and PTS) among children treated with conventional-duration (3 months total) anticoagulation differ between those with and without thrombus resolution/non-occlusion at 6 weeks.
Hypothesis: Among children with first-episode, provoked, acute venous thrombosis treated with conventional-duration (3 months total) anticoagulation, the cumulative incidences of recurrent VTE and PTS are significantly lower among those in whom thrombus resolution/non-occlusion was, versus was not, evident after the initial 6 weeks of anticoagulant therapy.
Specific Aim #4: To establish a clinical trial-derived plasma and nucleic acids biorepository for future proteomic, genomic, and metabolomic investigations of predictors and modulators of VTE outcomes in children.
Specific Aim #5: To investigate whether duration of anticoagulation (over the range of 3 months to indefinite duration, as determined clinically in routine care) on influences the risks of symptomatic recurrent VTE and clinically-relevant bleeding among children with first-episode, provoked, acute venous thrombosis in whom persistent antiphospholipid antibody (APA) positivity is evident at 6- and 12 -weeks post-diagnosis.
Hypothesis: Among children with first-episode, provoked, acute venous thrombosis in whom persistent APA positivity is evident at 6- and 12 -weeks post-diagnosis, duration of anticoagulant therapy is not a predictor of symptomatic recurrent VTE but is directly related to the risk of clinically-relevant bleeding.
Specific Aim #6 (Exploratory Aim): To evaluate whether the effect of treatment duration on the risks of symptomatic recurrent VTE and clinically-relevant bleeding in children with first-episode, provoked, acute venous thrombosis differs substantively between subgroups defined by type of sub-acute anticoagulant therapy in real-world clinical use (all prescribed clinically, with the exception of investigational dalteparin, which was prescribed under an investigator-held IND through December 2013).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Intervention: A
Patients with non-occlusive thrombus or resolved thrombosis at 6 weeks.
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.
Intervention: B
Patients with non-occlusive thrombus or resolved thrombosis at 6 weeks.
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.
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.
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
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.
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.
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. In the opinion of the investigator, the venous thrombosis was a provoked (i.e., non-spontaneous) event (e.g.: hospitalization; Central venous catheterization; infection; dehydration; surgery; trauma; immobility; use of estrogen-containing oral contraceptive pills; flare of autoimmune/rheumatologic condition).
Exclusion Criteria
2. Malignancy that, in the opinion of the treating oncologist, is not in remission (note: remission may exist on or off anti-neoplastic therapy)
3. Systemic lupus erythematosus
4. Pulmonary embolism that is not accompanied by DVT or is more proximal than segmental branches of the pulmonary artery
5. Use of, or intent to use, thrombolytic therapy
6. Chronic anticoagulant at prophylactic dosing is being or will be administered beyond 6 months post VTE diagnosis
7. Moderate/severe anticoagulant deficiency (defined by any one of the following):
1. protein C \<20 IU/dL if patient is ≥3 months of age, or protein C below lower limit of detection if patient is \<3 months of age;
2. antithrombin \<30 IU/dL if patient is ≥3 months of age, or antithrombin below lower limit of detection if patient is \<3 months of age;
3. protein S (free antigen or activity) \<20 IU/dL.
20 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Johns Hopkins All Children's Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Neil A Goldenberg, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins All Children's Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Alabama Birmingham
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Orange County
Orange, California, United States
Stanford Medicine
Palo Alto, California, United States
UC Davis Children's Center
Sacramento, California, United States
Rady Children's Hospital UCSD
San Diego, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Yale School of Medicine
New Haven, Connecticut, United States
George Washington University, Children's National Medical Center
Washington D.C., District of Columbia, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Emory University / Children's Healthcare of Atlanta
Atlanta, Georgia, United States
Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, United States
University of Iowa Stead Family Children's Hospital
Iowa City, Iowa, United States
Kosair Children's Hospital
Louisville, Kentucky, United States
Johns Hopkins Medicine
Baltimore, Maryland, United States
Boston Children's Hospital
Boston, Massachusetts, United States
Children's Hospital of Michigan, Wayne State University
Detroit, Michigan, United States
Michigan State University
East Lansing, Michigan, United States
Helen Devos Children's Hospital
Grand Rapids, Michigan, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Glacier View
Kalispell, Montana, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
Cornell University
Ithaca, New York, United States
Cohen Children's Medical Center
New Hyde Park, New York, United States
NewYork-Presbyterian
New York, New York, United States
Golisano Children's Hospital
Rochester, New York, United States
The Children's Hospital at Montefiore
The Bronx, New York, United States
Duke University
Durham, North Carolina, United States
Akron Children's Hospital
Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Oregon Health Sciences University
Portland, Oregon, United States
Hershey Medical Center
Hershey, Pennsylvania, United States
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Palmetto Health
Columbia, South Carolina, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, United States
University of Texas Southwestern
Dallas, Texas, United States
Texas Children's Hospital (Baylor)
Houston, Texas, United States
Primary Children's Medical Center
Salt Lake City, Utah, United States
University of Virginia Health System University Hospital
Charlottesville, Virginia, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Medical College of Wisconsin, Blood Center of Wisconsin
Wauwatosa, Wisconsin, United States
Royal Children's Hospital
Parkville, Victoria, Australia
Medizinishe Universitat Wien
Vienna, , Austria
Stollery Children's Hospital
Edmonton, Alberta, Canada
McMaster Childrens Hospital
Hamilton, Ontario, Canada
SickKids
Toronto, Ontario, Canada
Montreal Children's Hospital
Montreal, Quebec, Canada
Hadassah Hebrew-University Hospital
Jerusalem, , Israel
Sheba Medical Center
Tel Aviv, , Israel
Sophia Children's Hospital
Rotterdam, , Netherlands
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Betensky M, Mosha M, Tarango C, Verma A, Bhat R, Kucine NE, Nakano T, Nakar C, Woods G, Amankwah E, Brandao LR, Schulman S, Goldenberg NA. Outcomes in children with provoked venous thrombosis and antiphospholipid antibodies: findings from the Kids-DOTT trial. Blood Adv. 2024 Nov 26;8(22):5790-5795. doi: 10.1182/bloodadvances.2024014415.
Goldenberg NA, Tripputi M, Crowther M, Abshire TC, DiMichele D, Manco-Johnson MJ, Hiatt WR. The "parallel-cohort RCT": Novel design aspects and application in the Kids-DOTT trial of pediatric venous thromboembolism. Contemp Clin Trials. 2010 Jan;31(1):131-3. doi: 10.1016/j.cct.2009.11.006. Epub 2009 Nov 24.
Kittelson JM, Spyropoulos AC, Halperin JL, Kessler CM, Schulman S, Steg G, Turpie AG, Cutler NR, Hiatt WR, Goldenberg NA; Antithrombotic Trials Leadership and Steering (ATLAS) Group. Balancing risk and benefit in venous thromboembolism trials: concept for a bivariate endpoint trial design and analytic approach. J Thromb Haemost. 2013 Aug;11(8):1443-8. doi: 10.1111/jth.12324.
Goldenberg NA, Abshire T, Blatchford PJ, Fenton LZ, Halperin JL, Hiatt WR, Kessler CM, Kittelson JM, Manco-Johnson MJ, Spyropoulos AC, Steg PG, Stence NV, Turpie AG, Schulman S; Kids-DOTT Trial Investigators. Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): pilot/feasibility phase findings. J Thromb Haemost. 2015 Sep;13(9):1597-605. doi: 10.1111/jth.13038. Epub 2015 Aug 11.
Goldenberg NA, Kittelson JM, Abshire TC, Bonaca M, Casella JF, Dale RA, Halperin JL, Hamblin F, Kessler CM, Manco-Johnson MJ, Sidonio RF, Spyropoulos AC, Steg PG, Turpie AGG, Schulman S; Kids-DOTT Trial Investigators and the ATLAS Group. Effect of Anticoagulant Therapy for 6 Weeks vs 3 Months on Recurrence and Bleeding Events in Patients Younger Than 21 Years of Age With Provoked Venous Thromboembolism: The Kids-DOTT Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):129-137. doi: 10.1001/jama.2021.23182.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
https://www.hopkinsallchildrens.org/academics/research/multicenter-studies/kids-dott
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
IRB00063928
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.