Deep Vein ThrombosisPhase 3PHLONCT02767232
Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial
A Phase 3 study testing Recombinant tissue plasminogen activator (rt-PA) and Standard Anticoagulation Therapy in people with Deep Vein Thrombosis and Post-Thrombotic Syndrome, run by University of Colorado, Denver.
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… Read more about this study
- Who is it for?
- Ages 6 to 21 years
- Conditions the study is for
- Deep Vein Thrombosis, Post-Thrombotic Syndrome, Venous Thrombosis
- What is being tested?
- Recombinant tissue plasminogen activator (rt-PA) and Standard Anticoagulation Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2018to Jun 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
About this study
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.
Read the 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
- Being tested
- Recombinant tissue plasminogen activator (rt-PA), Standard Anticoagulation Therapy
- 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
- Medical subject headings
- Venous Thrombosis, Postthrombotic Syndrome, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant tissue plasminogen activator (rt-PA)Drug
Also called rt-PA, recombinant tissue plasminogen activator, Activase, Alteplase
Catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.
Standard Anticoagulation TherapyDrug
Standard anticoagulation determined by physician for a period of 3-6 months
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Recombinant tissue plasminogen activator (rt-PA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of Post-Thrombotic Syndrome (PTS)
Post-thrombotic syndrome (PTS) as determined by the Manco-Johnson Pediatric PTS Instrument
Measured: within 24 months after randomization
Secondary outcomes (6)
Change in Quality of Life (PedsQL)
Quality of life (QoL) as determined by the PedsQL(TM)
Measured: within 24 months of randomization
Change in Quality of Life (Peds-VEINES)
Quality of life (QoL) as determined by the Peds-VEINES-QoL
Measured: within 24 months of randomization
Assessment of Venous Valvular Reflux
Venous reflux will be assessed in a subset of patients using standard techniques
Measured: at 12 months post-diagnosis
Severity of Post-Thrombotic Syndrome (PTS)
Severity of PTS as determined by the Manco-Johnson PTS Instrument.
Measured: within 24 months of randomization
Time to Resolution of presenting Deep Vein Thrombosis (DVT) symptoms
Measured: within 24 months of randomization
Degree of clot lysis
Measured: within 24 months of randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2016 (estimated)
- Study startJul 2018 (estimated)
- Primary completionApr 2023 (estimated)
- Study completionJun 2023 (estimated)
Why it stopped: Did not receive NIH Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Deep Vein ThrombosisStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- RTI International, Mid America Heart Institute, National Heart, Lung, and Blood Institute (NHLBI), Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Marilyn J Manco-Johnson, MD, Principal investigator, University of Colorado Denver Anschutz Medical Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02767232
- Sponsor's protocol ID
- 14-0659
- Other IDs
- ML29463
- Acronym
- PHLO
- Status last verified
- Aug 2018
- First submitted
- 16 Dec 2015
- Last updated
- 10 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes Trial
- ClinicalTrials.gov ID
- NCT02767232
- Acronym / sponsor ID
- PHLO / 14-0659
- Keywords
- PHLO, deep vein thrombosis, deep venous thrombosis, blood clot, catheter-directed thrombolysis, thrombolysis, post-thrombotic syndrome, PTS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Did not receive NIH Funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- RTI International, Mid America Heart Institute, National Heart, Lung, and Blood Institute (NHLBI), Genentech, Inc.
- Study start
- Jul 2018 (estimated)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 10 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Anticoagulation Therapy | Active comparator | Drug: Standard Anticoagulation TherapyAnticoagulant 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. |
| Catheter-Directed Thrombolysis | Experimental | Drug: Recombinant tissue plasminogen activator (rt-PA)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 |
Who may qualify
- Ages
- 6 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant tissue plasminogen activator (rt-PA)Also: rt-PA, recombinant tissue plasminogen activator, Activase, AlteplaseCatheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device. | Drug | Catheter-Directed Thrombolysis |
| Standard Anticoagulation TherapyStandard anticoagulation determined by physician for a period of 3-6 months | Drug | Standard Anticoagulation Therapy |
Primary outcome
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
6 secondary outcomes
Change in Quality of Life (PedsQL)
Time frame: within 24 months of randomization
Change in Quality of Life (Peds-VEINES)
Time frame: within 24 months of randomization
Assessment of Venous Valvular Reflux
Time frame: at 12 months post-diagnosis
Severity of Post-Thrombotic Syndrome (PTS)
Time frame: within 24 months of randomization
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2018.
- Predictors of the Post Thrombotic Syndrome During Long-Term Treatment of Proximal Deep Vein ThrombosisLink provided by the sponsor.
- Deep Vein ThrombosisLink provided by the sponsor.
Related trials for Deep Vein Thrombosis
Active, not recruiting
This Research Proposal Focuses on Evaluating the Effectiveness of a Nursing Care Protocol in Preventing Deep Vein Thrombosis (DVT) in Patients Undergoing On-pump Cardiac Surgery. The Study Will Include an Intervention Group That Receives the Nursing Protocol and a Control Group That Receives Routine
On-pump Cardiac Surgery - Prevention - Intervention - Experimental Group - Control Group - Incidence - Complications, DVT - Deep Vein Thrombosis
Enrolling by invitationObservational study
ClotTriever® Thrombectomy System Use-Result Survey in Japan
Deep Vein Thrombosis
Not yet recruiting
SAFELY RULING OUT DEEP VEIN THROMBOSIS IN PREGNANCY WITH THE LEFt SCORE AND TRIMESTER-ADJUSTED D-DIMER CUTOFFS (the PREG-DVT Study): A PROSPECTIVE COHORT STUDY.
Pregnancy Related, Deep Vein Thrombosis
RecruitingObservational study
Cleaner Long-tErm Assessment Registry - Venous Insights and Efficacy With eXtended Tracking
Deep Vein Thrombosis (DVT), Thrombus in the Peripheral Venous Vasculature
Enrolling by invitation
Evaluating the Use of Grip Exercises to Decrease Deep Vein Thrombosis in Adult Patients With PICC Lines
Deep Vein Thrombosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marilyn J Manco-Johnson, MD principal investigator
University of Colorado Denver Anschutz Medical Campus
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Recombinant tissue plasminogen activator (rt-PA) and Standard Anticoagulation Therapy in people with Deep Vein Thrombosis and Post-Thrombotic Syndrome, run by University of Colorado, Denver.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of Post-Thrombotic Syndrome (PTS) (time frame: within 24 months after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2018.