Deep Vein Thrombosis, Post-Thrombotic Syndrome, Venous Thrombosis
Conditions
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
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
Interventions
Catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.
DRUGStandard Anticoagulation Therapy
Standard anticoagulation determined by physician for a period of 3-6 months
Sponsors
RTI International
Mid America Heart Institute
National Heart, Lung, and Blood Institute (NHLBI)
Genentech, Inc.
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of Post-Thrombotic Syndrome (PTS) | within 24 months after randomization | Post-thrombotic syndrome (PTS) as determined by the Manco-Johnson Pediatric PTS Instrument |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life (Peds-VEINES) | within 24 months of randomization | Quality of life (QoL) as determined by the Peds-VEINES-QoL |
| Change in Quality of Life (PedsQL) | within 24 months of randomization | Quality of life (QoL) as determined by the PedsQL(TM) |
| Assessment of Venous Valvular Reflux | at 12 months post-diagnosis | Venous reflux will be assessed in a subset of patients using standard techniques |
| Severity of Post-Thrombotic Syndrome (PTS) | within 24 months of randomization | Severity of PTS as determined by the Manco-Johnson PTS Instrument. |
| Time to Resolution of presenting Deep Vein Thrombosis (DVT) symptoms | within 24 months of randomization | — |
| Degree of clot lysis | within 24 months of randomization | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Recurrence of Venous Thromboembolism | within 7 days and 24 months after randomization | — |
| Death | within 7 days and 24 months after randomization | — |
| Cost-Effectiveness | within 24 months after randomization | Cost-effectiveness of CDT followed by anticoagulation relative to anticoagulation alone will be measured via hospital bills, UB-04 summary bills, and EQ-5D-Y. |
| Development of Symptomatic Pulmonary Embolism | within 7 days and 24 months after randomization | — |
| Development of Major Bleeding | within 7 days and 24 months after randomization | — |
Outcome results
None listed