Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial

Deep Vein Thrombosis Clinical Trial

— PHLO  

Official title:

Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02767232
• Other study ID #: 14-0659
• Secondary ID: ML29463
• Status: Withdrawn
• Phase: Phase 3
• Start date: July 2018
• Est. completion date: June 2023

Study information

• Verified date: August 2018
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Deep Vein Thrombosis
• Post-Thrombotic Syndrome
• Postphlebitic Syndrome
• Postthrombotic Syndrome
• Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Recombinant tissue plasminogen activator (rt-PA)
Catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.
• Standard Anticoagulation Therapy
Standard anticoagulation determined by physician for a period of 3-6 months

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
University of Colorado, Denver	Genentech, Inc., Mid America Heart Institute, National Heart, Lung, and Blood Institute (NHLBI), RTI International

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Development of Major Bleeding		within 7 days and 24 months after randomization
Other	Development of Symptomatic Pulmonary Embolism		within 7 days and 24 months after randomization
Other	Recurrence of Venous Thromboembolism		within 7 days and 24 months after randomization
Other	Death		within 7 days and 24 months after randomization
Other	Cost-Effectiveness	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.	within 24 months after randomization
Primary	Development of Post-Thrombotic Syndrome (PTS)	Post-thrombotic syndrome (PTS) as determined by the Manco-Johnson Pediatric PTS Instrument	within 24 months after randomization
Secondary	Change in Quality of Life (PedsQL)	Quality of life (QoL) as determined by the PedsQL(TM)	within 24 months of randomization
Secondary	Change in Quality of Life (Peds-VEINES)	Quality of life (QoL) as determined by the Peds-VEINES-QoL	within 24 months of randomization
Secondary	Assessment of Venous Valvular Reflux	Venous reflux will be assessed in a subset of patients using standard techniques	at 12 months post-diagnosis
Secondary	Severity of Post-Thrombotic Syndrome (PTS)	Severity of PTS as determined by the Manco-Johnson PTS Instrument.	within 24 months of randomization
Secondary	Time to Resolution of presenting Deep Vein Thrombosis (DVT) symptoms		within 24 months of randomization
Secondary	Degree of clot lysis		within 24 months of randomization

External Links

•   Deep Vein Thrombosis
•   Predictors of the Post Thrombotic Syndrome During Long-Term Treatment of Proximal Deep Vein Thrombosis
•   The Long-Term Clinical Course of Acute Deep Vein Thrombosis