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Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial (PHLO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02767232
Recruitment Status : Withdrawn (Did not receive NIH Funding)
First Posted : May 10, 2016
Last Update Posted : August 10, 2018
Sponsor:
Collaborators:
RTI International
Mid America Heart Institute
National Heart, Lung, and Blood Institute (NHLBI)
Genentech, Inc.
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE December 16, 2015
First Posted Date  ICMJE May 10, 2016
Last Update Posted Date August 10, 2018
Estimated Study Start Date  ICMJE July 2018
Estimated Primary Completion Date April 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2016)
Development of Post-Thrombotic Syndrome (PTS) [ Time Frame: within 24 months after randomization ]
Post-thrombotic syndrome (PTS) as determined by the Manco-Johnson Pediatric PTS Instrument
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02767232 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2016)
  • Change in Quality of Life (PedsQL) [ Time Frame: within 24 months of randomization ]
    Quality of life (QoL) as determined by the PedsQL(TM)
  • Change in Quality of Life (Peds-VEINES) [ Time Frame: within 24 months of randomization ]
    Quality of life (QoL) as determined by the Peds-VEINES-QoL
  • Assessment of Venous Valvular Reflux [ Time Frame: at 12 months post-diagnosis ]
    Venous reflux will be assessed in a subset of patients using standard techniques
  • Severity of Post-Thrombotic Syndrome (PTS) [ Time Frame: 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 [ Time Frame: within 24 months of randomization ]
  • Degree of clot lysis [ Time Frame: within 24 months of randomization ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 6, 2016)
  • Development of Major Bleeding [ Time Frame: within 7 days and 24 months after randomization ]
  • Development of Symptomatic Pulmonary Embolism [ Time Frame: within 7 days and 24 months after randomization ]
  • Recurrence of Venous Thromboembolism [ Time Frame: within 7 days and 24 months after randomization ]
  • Death [ Time Frame: within 7 days and 24 months after randomization ]
  • Cost-Effectiveness [ Time Frame: 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial
Official Title  ICMJE Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Deep Vein Thrombosis
  • Post-Thrombotic Syndrome
  • Venous Thrombosis
Intervention  ICMJE
  • Drug: Recombinant tissue plasminogen activator (rt-PA)
    Catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.
    Other Names:
    • rt-PA
    • recombinant tissue plasminogen activator
    • Activase
    • Alteplase
  • Drug: Standard Anticoagulation Therapy
    Standard anticoagulation determined by physician for a period of 3-6 months
Study Arms  ICMJE
  • Active Comparator: 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.
    Intervention: Drug: Standard Anticoagulation Therapy
  • Experimental: 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
    Intervention: Drug: Recombinant tissue plasminogen activator (rt-PA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 8, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: May 6, 2016)
270
Estimated Study Completion Date  ICMJE June 2023
Estimated Primary Completion Date April 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02767232
Other Study ID Numbers  ICMJE 14-0659
ML29463 ( Other Identifier: Genentech, Inc. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE
  • RTI International
  • Mid America Heart Institute
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Marilyn J Manco-Johnson, MD University of Colorado Denver Anschutz Medical Campus
PRS Account University of Colorado, Denver
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP