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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02767232|
Recruitment Status : Not yet recruiting
First Posted : May 10, 2016
Last Update Posted : September 20, 2017
|Condition or disease||Intervention/treatment||Phase|
|Deep Vein Thrombosis Post-Thrombotic Syndrome Venous Thrombosis||Drug: Recombinant tissue plasminogen activator (rt-PA) Drug: Standard Anticoagulation Therapy||Phase 3|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||270 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial|
|Estimated Study Start Date :||July 2018|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||June 2023|
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.
Drug: Standard Anticoagulation Therapy
Standard anticoagulation determined by physician for a period of 3-6 months
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
Drug: Recombinant tissue plasminogen activator (rt-PA)
Catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.
- 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
- 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 ]
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02767232
|Contact: Julie A Smith, BS||303-724-6187||Julie.Smith@ucdenver.edu|
|Contact: Donna M Oscepinski, MBA||303-724-0365||Donna.Oscepinski@ucdenver.edu|
|Principal Investigator:||Marilyn J Manco-Johnson, MD||University of Colorado Denver Anschutz Medical Campus|