Clinical trial NCT02767232: Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial
Official title: Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Deep Vein Thrombosis
Post-Thrombotic Syndrome
Venous Thrombosis
Keywords: PHLO
deep vein thrombosis
deep venous thrombosis
blood clot
catheter-directed thrombolysis
thrombolysis
post-thrombotic syndrome
PTS
recombinant tissue plasminogen activator
rt-PA
Activase
Alteplase
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: RTI International
name: Mid America Heart Institute
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Genentech, Inc.
First posted: 2016-05-10
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the use of adjunctive catheter-directed thrombolysis (CDT), which includes the intrathrombus administration of rt-PA (Activase/Alteplase), can prevent post-thrombotic syndrome (PTS) in pediatric patients with symptomatic proximal deep vein thrombosis (DVT) as compared with optimal standard anticoagulation alone.

Detailed description: rt-PA, the study drug, is a fibrinolytic drug that is indicated for use in acute myocardial infarction, acute ischemic stroke, and acute massive pulmonary embolism in adults. Previous studies have shown the ability of rt-PA to lyse venous thrombus in patients with deep vein thrombosis (DVT), and suggest that successful rt-PA mediated thrombolysis can prevent post-thrombotic syndrome (PTS).

rt-PA is delivered directly into venous thrombus using a catheter/device which is embedded within the thrombus by a physician under imaging guidance. This method of rt-PA delivery, catheter-directed thrombolysis (CDT), is thought to be safer, more effective, and more efficient than previous methods. The question of whether CDT using rt-PA improves long-term DVT patient outcomes with acceptable risk and cost is currently being studied in the ATTRACT Trial for adults, but has not yet been addressed in the pediatric population.

The rationale for performing the PHLO Trial is based upon:

* the major burden of PTS on pediatric DVT patients and the U.S. healthcare system
* the reported association between rapid clot lysis and prevention of PTS
* the proven ability of rt-PA to dissolve venous thrombus in proximal DVT
* the recent advances in CDT methods which may lower bleeding risk, but which could, inadvertently, cause more endothelial injury in the smaller caliber vessels of pediatric patients
* the lack of outcome evidence for either anticoagulation or catheter-directed thrombolysis in children
* the major clinical controversy on whether CDT should routinely be used for first-line DVT therapy

Eligibility criteria: Inclusion Criteria:

* Subject and/or legal guardian has voluntarily provided signed informed consent.
* Subject is 6-21 years old with a minimum weight of 20 kg at the time of enrollment.
* Radiologically-confirmed, symptomatic proximal lower extremity DVT involving the inferior vena cava, iliac vein, and/or common femoral vein; DVT must be occlusive in at least one involved vein
* Life expectancy greater than or equal to 2 years.

Exclusion Criteria:

* Symptom duration \> 14 days for DVT episode in affected leg
* Known history of a bleeding disorder
* Known history of heparin-induced thrombocytopenia (HIT)
* Prior established diagnosis of PTS in lower extremities
* Circulatory compromise necessitating surgery
* Pulmonary embolism with hemodynamic compromise or other acute illness precluding tolerance of catheter-directed therapy
* Severe hypersensitivity or allergy to Activase(R), iodinated contrast or planned treatment anticoagulant drug, except for mild-moderate contrast allergies for which steroid pre-treatment can be used.
* Inability to maintain hemoglobin \<9.0 mg/dL, INR \>1.7, or platelets \<100,000/mL, using transfusion as indicated.
* Active or historic bleeding, vasculopathy, coagulopathy, invasive procedure or medical condition contraindicating thrombolysis or anticoagulation
* Previous thrombolysis within the last month
* Pregnant female or within 7 days of uncomplicated delivery
* Participation in another investigational study within the last month
* Life expectancy \< 2 years or with chronic non-ambulatory status
* Inability to provide informed consent or to comply with study assessments

Primary outcomes:
measure: Development of Post-Thrombotic Syndrome (PTS)
timeFrame: within 24 months after randomization
Secondary outcomes:
measure: Change in Quality of Life (PedsQL)
timeFrame: within 24 months of randomization
measure: Change in Quality of Life (Peds-VEINES)
timeFrame: within 24 months of randomization
measure: Assessment of Venous Valvular Reflux
timeFrame: at 12 months post-diagnosis
measure: Severity of Post-Thrombotic Syndrome (PTS)
timeFrame: within 24 months of randomization
measure: Time to Resolution of presenting Deep Vein Thrombosis (DVT) symptoms
timeFrame: within 24 months of randomization
measure: Degree of clot lysis
timeFrame: within 24 months of randomization
Other outcomes:
measure: Development of Major Bleeding
timeFrame: within 7 days and 24 months after randomization
measure: Development of Symptomatic Pulmonary Embolism
timeFrame: within 7 days and 24 months after randomization
measure: Recurrence of Venous Thromboembolism
timeFrame: within 7 days and 24 months after randomization
measure: Death
timeFrame: within 7 days and 24 months after randomization
measure: Cost-Effectiveness
timeFrame: within 24 months after randomization
Locations:
Study officials:
affiliation: University of Colorado Denver Anschutz Medical Campus
name: Marilyn J Manco-Johnson, MD
role: PRINCIPAL_INVESTIGATOR
References: