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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Venous Thrombosis	Other: Shortened duration (6 weeks) of anticoagulant therapy; Other: Conventional duration (3 months) of anticoagulant therapy; Other: No Intervention	Phase 3

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	815 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Prospective Multi-Center Evaluation of the Duration of Therapy for Thrombosis in Children
Study Start Date :	March 2008
Estimated Primary Completion Date :	June 30, 2021
Estimated Study Completion Date :	June 30, 2022

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 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.

Outcome Measures

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Primary Outcome Measures :

1. Bivariate endpoint. [ Time Frame: 1 Year ]

   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 :

1. Prevalence/severity of post-thrombotic syndrome. [ Time Frame: 1 and 2 Years ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	up to 20 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

1. Prior episode of VTE
2. Malignancy that, in the opinion of the treating oncologist, is not in remission, or for which chronic anticoagulation is being administered/anticipated to be initiated within 6 months (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. History of congenital cardiac disease for which chronic anticoagulation is being administered/ anticipated to be initiated within 6 months (e.g., for select patients or centers, in the setting of a single or hypoplastic ventricle or surgically-established cardiac shunt)

7. Moderate/severe anticoagulant deficiency as 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.

Contacts and Locations

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Contacts

Contact: Neil A Goldenberg, MD, PhD	727-767-6886	neil@jhmi.edu
Contact: Frances L Hamblin, MSHS, RN	727-767-2460	Frances.Hamblin@jhmi.edu

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Sponsors and Collaborators

Johns Hopkins All Children's Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Neil A Goldenberg, MD, PhD	Johns Hopkins All Children's Hospital

More Information

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Additional Information:

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

Publications:

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. Review.

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.

Responsible Party:	Neil Goldenberg, Director of Research and Chief Research Officer, Johns Hopkins All Children's Hospital, Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00687882 History of Changes
Other Study ID Numbers:	IRB00063928; 1U01HL130048-01A1 ( U.S. NIH Grant/Contract )
First Posted:	June 2, 2008
Last Update Posted:	March 20, 2018
Last Verified:	March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Neil Goldenberg, Johns Hopkins University:

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

Additional relevant MeSH terms:

Thrombosis; Venous Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases	Antibodies; Antibodies, Antiphospholipid; Anticoagulants; Immunologic Factors; Physiological Effects of Drugs