Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial

NCT ID: NCT02767232

Last Updated: 2018-08-10

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-31
• Study Completion Date: 2023-06-30

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

Conditions

Deep Vein Thrombosis; Post-Thrombotic Syndrome; Venous Thrombosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Anticoagulation Therapy

Anticoagulant therapy will be prescribed in accordance with 2012 ACCP Guidelines for children. Initial therapy generally will consist of low molecular weight heparin (LMWH) or unfractionated heparin (UFH), monitored to achieve and maintain a target anti-Xa activity of 0.5-1.0 IU/mL for LMWH and 0.35-0.7 IU/mL for UFH. Long-term therapy generally will consist of warfarin/coumadin, monitored to achieve and maintain a target INR of 2.0-3.0. The use of novel anticoagulants is permitted based on investigator preference.

Group Type: ACTIVE_COMPARATOR

Standard Anticoagulation Therapy

Intervention Type: DRUG

Standard anticoagulation determined by physician for a period of 3-6 months

Catheter-Directed Thrombolysis

Catheter-Directed Thrombolysis (CDT) with intrathrombus delivery of Recombinant tissue plasminogen activator (rt-PA) (maximum allowable total dose 35 mg/24 hours) into the DVT over a period of up to 24 hours. CDT will be initiated within 72 hours of diagnosis. Two methods of initial rt-PA delivery will be used: 1.) AngioJet Thrombectomy System- maximum first-session rt-PA dose 25 mg; or 2.) Catheter-directed rt-PA infusion for up to 24 hours at 0.01 mg/kg/hr (maximum 1.0 mg/hr) via a multisidehole catheter. Before and after CDT, patients will receive standard DVT therapy as in the standard anticoagulation group

Group Type: EXPERIMENTAL

Recombinant tissue plasminogen activator (rt-PA)

Intervention Type: DRUG

Catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.

Interventions

Recombinant tissue plasminogen activator (rt-PA)

Catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.

Intervention Type: DRUG

Standard Anticoagulation Therapy

Standard anticoagulation determined by physician for a period of 3-6 months

Intervention Type: DRUG

Other Intervention Names

rt-PA; recombinant tissue plasminogen activator; Activase; Alteplase

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RTI International

OTHER

Sponsor Role: collaborator

Mid America Heart Institute

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marilyn J Manco-Johnson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado Denver Anschutz Medical Campus

Related Links

http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2005.01216.x/abstract

Predictors of the Post Thrombotic Syndrome During Long-Term Treatment of Proximal Deep Vein Thrombosis

http://patient.info/health/deep-vein-thrombosis-leaflet

Deep Vein Thrombosis

Other Identifiers

ML29463

Identifier Type: OTHER

Identifier Source: secondary_id

14-0659

Identifier Type: -

Identifier Source: org_study_id