Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial

NCT02767232 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: 14-0659ML29463
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change in Quality of Life (PedsQL)

  within 24 months of randomization

• Change in Quality of Life (Peds-VEINES)

  within 24 months of randomization

• Assessment of Venous Valvular Reflux

  at 12 months post-diagnosis

• Severity of Post-Thrombotic Syndrome (PTS)

  within 24 months of randomization

• Time to Resolution of presenting Deep Vein Thrombosis (DVT) symptoms

  within 24 months of randomization

Other Outcomes (5)

• Development of Major Bleeding

  within 7 days and 24 months after randomization

• Development of Symptomatic Pulmonary Embolism

  within 7 days and 24 months after randomization

• Recurrence of Venous Thromboembolism

  within 7 days and 24 months after randomization

Study Arms (2)

Standard Anticoagulation Therapy

ACTIVE COMPARATOR

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.

Drug: Standard Anticoagulation Therapy

Catheter-Directed Thrombolysis

EXPERIMENTAL

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

Drug: Recombinant tissue plasminogen activator (rt-PA)

Interventions

Recombinant tissue plasminogen activator (rt-PA) DRUG

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

Also known as: rt-PA, recombinant tissue plasminogen activator, Activase, Alteplase

Catheter-Directed Thrombolysis

Standard Anticoagulation Therapy DRUG

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

Standard Anticoagulation Therapy

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• RTI International: collaborator
• Mid America Heart Institute: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Genentech, Inc.: collaborator

Related Links

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

MeSH Terms

Conditions

Venous Thrombosis; Postthrombotic Syndrome; Thrombosis

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Venous Insufficiency

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Marilyn J Manco-Johnson, MD

  University of Colorado Denver Anschutz Medical Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: May 10, 2016
• Study Start: July 1, 2018
• Primary Completion: April 1, 2023
• Study Completion: June 1, 2023
• Last Updated: August 10, 2018

Record last verified: 2018-08