Thrombosis Outcomes in Pediatric Venous Thromboembolism (TOP)

Predicting and Preventing Poor Outcomes of Venous Thromboembolism in Children

'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.

Study Overview

• Status: Active, not recruiting
• Conditions: 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 Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postthrombotic syndrome (PTS)	PTS as assessed by the validated Manco-Johnson and the modified Villata PTS instruments determined a priori and confirmed by an endpoint adjudicating committee	within 24 months after diagnosis of VTE
Symptomatic recurrent venous thromboembolism	Recurrent VTE as assessed by ISTH proposed recurrent VTE clinical criteria	within 24 months after diagnosis of VTE
Post-pulmonary embolism (PE) impairment	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)	within 24 months after diagnosis of VTE

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Physical Activity scores	Physical activity as determined by Gordin questionnaire	Within 24 months after diagnosis of VTE
Elastic Compression Stocking (ECS) use over time	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)	Within 24 months after diagnosis of VTE
Loss of venous access	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	12 months post DVT diagnosis
Venous valvular reflux	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	12 months post DVT diagnosis

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Ayesha Zia, M.D., University of Texas Southwestern Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: February 22, 2017
• First Submitted That Met QC Criteria: March 1, 2017
• First Posted (Actual): March 3, 2017

Study Record Updates

• Last Update Posted (Actual): June 23, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Deep Vein Thrombosis; Upper Extremity; anticoagulation; coagulation; Lower Extremity; Pulmonary Embolism; Chronic thromboembolic pulmonary hypertension; thrombin; fibrinolysis; Blood clot; Portal vein; Cerebral sinus; Renal vein; Post trombotic syndrome; Post pulmonary embolism syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism
• Other Study ID Numbers: STU 122015-029; 1K23HL132054-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No