Evaluation of the Duration of Therapy for Thrombosis in Children

NCT00687882 | Completed Phase 3 Results DMC

• 2 other identifiers: IRB000639281U01HL130048-01A1
• Study Type: interventional
• Target: 532
• Locations: 5 countries
• Sites: 62

Brief Summary

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.

Conditions

Venous Thrombosis

Keywords

Venous Thromboembolism; Postthrombotic Syndrome; Antithrombotic Therapy; Duration of Therapy; Children

Outcome Measures

Primary Outcomes (2)

• Efficacy Outcome - Occurrence of Symptomatic Recurrent Venous Thromboembolism

  Occurrence of symptomatic recurrent venous thromboembolism. Primary safety endpoint is occurrence of clinically-relevant bleeding (major + clinically-relevant non-major) bleeding.

  1 Year

• Safety Outcome - Occurrence of Clinically-relevant (i.e. Major Plus Clinically-relevant Non-major (CRNM)

  Occurrence of clinically-relevant (i.e. major plus clinically-relevant non-major (CRNM) bleeding

  1 year

Secondary Outcomes (3)

• Efficacy Outcome 1 - Occurrence of Symptomatic Recurrent Venous Thromboembolism (VTE) or Development of Post Thrombotic Syndrome (PTS) (Composite Endpoint)

  1 year

• Efficacy Outcome 2 - Occurrence of Symptomatic Recurrent Venous Thromboembolism (VTE)

  2 years

• Efficacy Outcome 3 - Development of Post Thrombotic Syndrome (PTS)

  1 year

Study Arms (4)

Intervention: A

EXPERIMENTAL

Patients with non-occlusive thrombus or resolved thrombosis at 6 weeks.

Other: Shortened duration (6 weeks) of anticoagulant therapy

Intervention: B

ACTIVE COMPARATOR

Patients with non-occlusive thrombus or resolved thrombosis at 6 weeks.

Other: Conventional duration (3 months) of anticoagulant therapy

Parallel Cohort: Persistent Occlusive Thrombosis

OTHER

Patients with completely occlusive thrombosis at 6 weeks.

Other: No Intervention

Parallel Cohort: Persistent Antiphospholipid Antibody

OTHER

Patients with persistent Positive Antiphospholipid Antibody at 6 weeks.

Other: No Intervention

Interventions

Shortened duration (6 weeks) of anticoagulant therapy OTHER

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: A

Conventional duration (3 months) of anticoagulant therapy OTHER

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.

Intervention: B

No Intervention OTHER

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 Occlusive Thrombosis

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children (birth to \<21 years of age) with radiologically-confirmed acute deep venous thrombosis in the past 30 days
• 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).

You may not qualify if:

• Prior episode of VTE
• Malignancy that, in the opinion of the treating oncologist, is not in remission (note: remission may exist on or off anti-neoplastic therapy)
• Systemic lupus erythematosus
• Pulmonary embolism that is not accompanied by DVT or is more proximal than segmental branches of the pulmonary artery
• Use of, or intent to use, thrombolytic therapy
• Chronic anticoagulant at prophylactic dosing is being or will be administered beyond 6 months post VTE diagnosis
• Moderate/severe anticoagulant deficiency (defined by any one of the following):
• 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;
• 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;
• protein S (free antigen or activity) \<20 IU/dL.

Sponsors & Collaborators

• Johns Hopkins All Children's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (63)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Orange County

Orange, California, 92868, United States

Location

Stanford Medicine

Palo Alto, California, 34304, United States

Location

UC Davis Children's Center

Sacramento, California, 95817, United States

Location

Rady Children's Hospital UCSD

San Diego, California, 92123, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

George Washington University, Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami

Miami, Florida, 33124, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Emory University / Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins Medicine

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Michigan, Wayne State University

Detroit, Michigan, 48201, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Helen Devos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Glacier View

Kalispell, Montana, 59901, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Cornell University

Ithaca, New York, 14850, United States

Location

Cohen Children's Medical Center

New Hyde Park, New York, 11040, United States

Location

NewYork-Presbyterian

New York, New York, 10032, United States

Location

Golisano Children's Hospital

Rochester, New York, 14642, United States

Location

The Children's Hospital at Montefiore

The Bronx, New York, 10467-2403, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Palmetto Health

Columbia, South Carolina, 29203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Texas Children's Hospital (Baylor)

Houston, Texas, 77030, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 81432, United States

Location

University of Virginia Health System University Hospital

Charlottesville, Virginia, 22903, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Medical College of Wisconsin, Blood Center of Wisconsin

Wauwatosa, Wisconsin, 53226, United States

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Medizinishe Universitat Wien

Vienna, Austria

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

McMaster Childrens Hospital

Hamilton, Ontario, Canada

Location

SickKids

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Hadassah Hebrew-University Hospital

Jerusalem, Israel

Location

Sheba Medical Center

Tel Aviv, Israel

Location

Sophia Children's Hospital

Rotterdam, Netherlands

Location

Related Publications (5)

• 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.

  PMID: 19941974 BACKGROUND

• 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.

  PMID: 23773172 BACKGROUND

• 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.

  PMID: 26118944 BACKGROUND

• 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.

  PMID: 39321425 DERIVED

• 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.

  PMID: 35015038 DERIVED

Related Links

• https://www.hopkinsallchildrens.org/academics/research/multicenter-studies/kids-dott

MeSH Terms

Conditions

Venous Thrombosis; Venous Thromboembolism; Postthrombotic Syndrome

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thromboembolism; Venous Insufficiency

Limitations and Caveats

1. Small population of patients with cancer or pulmonary embolism 2. The anticoagulant therapies prescribed were predominantly Low Molecular Weight Heparin (LMWH), vs. oral anticoagulant therapies 3. Trade-offs between recurrent VT and current relevant bleeds 4. The secondary noninferiority analyses involving chronic venous insufficiency were solely descriptive 5. Low frequency pediatric disease with limitations 6. Small number of primary and efficacy and safety events

Results Point of Contact

• Title: Dr. Neil A Goldenberg, Associate Dean of Research
• Organization: Johns Hopkins All Children's Hospital

neil@jhmi.edu

727-767-3674

Study Officials

• Neil A Goldenberg, MD, PhD

  Johns Hopkins All Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2008
• First Posted: June 2, 2008
• Study Start: March 1, 2008
• Primary Completion: January 5, 2021
• Study Completion: February 15, 2022
• Last Updated: June 18, 2025
• Results First Posted: June 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CA (4); NL (1); IL (2); US (54)