Thrombosis Outcomes in Pediatric Venous Thromboembolism (TOP)

• ClinicalTrials.gov Identifier: NCT03068923
• Recruitment Status: Active, not recruiting
• First Posted: March 3, 2017
• Last Update Posted: May 19, 2020
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): University of Texas Southwestern Medical Center

Study Description

Brief Summary:

'The TOP Study' is a prospective cohort study whose main objective is to develop better prognostic biomarkers and identify children at risk of adverse thrombotic outcomes very early in the course after an initial venous thromboembolic events (VTE). The study will compare biomarkers in children that develop poor VTE outcomes (such as recurrence, postthrombotic syndrome and post PE impairment ) after an initial VTE with those that do not develop such outcomes.

Condition or disease
Venous Thromboembolism

Detailed Description:

All newly diagnosed patients with a first radiologically confirmed thrombotic event (any site) diagnosed at Children's Medical Center, Dallas will be followed prospectively with global coagulation assessment over a 24-month period, and monitored for development of carefully defined adverse VTE outcomes in a blinded manner. Biomarker assessment will include global coagulation assays (thrombin generation assay and modified thromboelastography to study fibrinolysis) at 3, 6, 12, 18 and 24 months post VTE diagnosis.

Study Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Predicting and Preventing Poor Outcomes of Venous Thromboembolism in Children
• Actual Study Start Date: May 2016
• Estimated Primary Completion Date: February 2022
• Estimated Study Completion Date: February 2023

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Postthrombotic syndrome (PTS) [ Time Frame: within 24 months after diagnosis of VTE ]
   PTS as assessed by the validated Manco-Johnson and the modified Villata PTS instruments determined a priori and confirmed by an endpoint adjudicating committee
2. Symptomatic recurrent venous thromboembolism [ Time Frame: within 24 months after diagnosis of VTE ]
   Recurrent VTE as assessed by ISTH proposed recurrent VTE clinical criteria
3. Post-pulmonary embolism (PE) impairment [ Time Frame: within 24 months after diagnosis of VTE ]
   Post-PE impairment, defined as deterioration (compared to discharge or previous follow-up visit), or persistence, in a) echocardiographic parameters of right ventricular (RV) dysfunction (defined by abnormal RV basal diameter or abnormal right atrial end systolic area or abnormal tricuspid annular plane systolic excursion or presence of pericardial effusion) and/or pulmonary hypertension (defined by abnormal estimated right atrial pressure or elevated systolic tricuspid regurgitant velocity), and clinical, functional parameters of RV failure (new appearance of symptoms of heart failure or abnormal six-minute walking distance or elevated brain natriuretic peptide (BNP) plasma levels or abnormal peak O2 uptake on cardiopulmonary exercise testing)

Secondary Outcome Measures :

1. Post-thrombotic sequelae [ Time Frame: Within 24 months after diagnosis of VTE ]
   Site specific sequelae after cerebral sinus venous, portal vein and renal vein thrombosis as assessed by ISTH recommended guidelines
2. Change in quality of life [ Time Frame: Within 24 months after diagnosis of VTE ]
   Quality of life by PedsQL (TM)

Other Outcome Measures:

1. Change in Physical Activity scores [ Time Frame: Within 24 months after diagnosis of VTE ]
   Physical activity as determined by Gordin questionnaire
2. Elastic Compression Stocking (ECS) use over time [ Time Frame: Within 24 months after diagnosis of VTE ]
   ECS use will be assessed by ECS log/diary documenting dedicated (use for at least 6 days/week), moderate (use for 4-5 days/week) or poor use (<4 days/week)
3. Loss of venous access [ Time Frame: 12 months post DVT diagnosis ]
   Loss of venous access in subjects with catheter related DVT of the upper extremity DVT as defined by >30% of the narrowing of the involved vein as assessed by doppler ultrasound or contrast venography
4. Venous valvular reflux [ Time Frame: 12 months post DVT diagnosis ]
   Venous valvular reflux in subjects with lower extremity DVT will be assessed as present (>0.5 seconds) or absent (<0.5 seconds) at the 12 month post diagnosis visit with a standardized venous reflux ultrasound procedure

Biospecimen Retention:   Samples With DNA

Plasma and DNA samples

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed patients with first venous thromboembolism who have completed therapeutic anticoagulant therapy

Criteria

Inclusion Criteria:

• Boys and girls age birth (0 years) to equal to or less than 21 years
• A radiologically confirmed first venous thromboembolism episode (both extremity and non-extremity) who have completed anticoagulation therapy as per the 9th edition of the ACCP guidelines

Exclusion Criteria:

• Known malignancy
• Pregnancy or immediate post-partum period (12 weeks after delivery)
• Sickle cell disease
• Known bleeding disorder

Contacts and Locations

Locations

United States, Texas

Children's Medical Center

Dallas, Texas, United States, 75235

Sponsors and Collaborators

University of Texas Southwestern Medical Center

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Ayesha Zia, M.D.; University of Texas Southwestern Medical Center

More Information

Publications of Results:

Zia A, Russell J, Sarode R, Veeram SR, Josephs S, Malone K, Zhang S, Journeycake J. Markers of coagulation activation, inflammation and fibrinolysis as predictors of poor outcomes after pediatric venous thromboembolism: A systematic review and meta-analysis. Thromb Res. 2017 Dec;160:1-8. doi: 10.1016/j.thromres.2017.10.003. Epub 2017 Oct 7. Review.

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT03068923
• Other Study ID Numbers: STU 122015-029; 1K23HL132054-01 ( U.S. NIH Grant/Contract )
• First Posted: March 3, 2017
• Last Update Posted: May 19, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Texas Southwestern Medical Center:

Blood clot; Deep Vein Thrombosis; Pulmonary Embolism; Lower Extremity; Upper Extremity; Cerebral sinus; Renal vein; Portal vein; thrombin; fibrinolysis; coagulation; anticoagulation; Post trombotic syndrome; Post pulmonary embolism syndrome; Chronic thromboembolic pulmonary hypertension

Additional relevant MeSH terms:

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