<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04411316</url>
  </required_header>
  <id_info>
    <org_study_id>300439</org_study_id>
    <nct_id>NCT04411316</nct_id>
  </id_info>
  <brief_title>Catheter-directed Thrombolysis Compared to Anticoagulation Alone for Acute Primary Iliofemoral Deep Venous Thrombosis</brief_title>
  <official_title>Pharmacomechanical Catheter-directed Thrombolysis (PCDT) Plus Anticoagulation Compared to Anticoagulation Alone for Acute Primary Iliofemoral Deep Venous Thrombosis:</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Toledo Health Science Campus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Toledo</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Post-thrombotic syndrome (PTS) is a complication that can develop after deep vein thrombosis&#xD;
      (DVT) of the lower extremities. PTS can occur at various times after the initial episode, but&#xD;
      usually manifests within two years of initial DVT onset. Early and more complete thrombus&#xD;
      clearance is believed by many to relieve venous outflow obstruction, preserve valvular&#xD;
      function and reduce venous hypertension. Two previously published randomized controlled&#xD;
      trials, the CAVENT trial and the ATTRACT trial, were larger and designed to investigate the&#xD;
      efficacy of CDT. However, both of these trials included patients with iliofemoral as well as&#xD;
      femoro-popliteal deep vein thrombosis. Our study will be limited to patients with iliofemoral&#xD;
      deep vein thrombosis to assess whether Pharmacomechanical catheter-directed thrombolysis&#xD;
      (PCDT) therapy utilizing AngioJet and tPA can safely and effectively reduce post thrombotic&#xD;
      syndrome after 24 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with Iliofemoral DVT are theoretically at the highest risk for development of PRS&#xD;
      given involvement of the major drainage pathway of both superficial femoral and deep femoral&#xD;
      veins. This would not only affect the primary venous drainage, but would also compromise the&#xD;
      ability to develop efficient collateral pathways. This creates higher chances of developing&#xD;
      post-thrombotic syndrome (PTS). The proposed trial would utilize Angiojet thrombectomy&#xD;
      followed by catheter directed thrombolysis and Anticoagulation compared to Anticoagulation&#xD;
      alone. To assess whether Pharmacomechanical catheter-directed thrombolysis (PCDT) therapy&#xD;
      utilizing AngioJet and tPA for the treatment of iliofemoral deep venous thrombosis can safely&#xD;
      and effectively reduce post thrombotic syndrome after 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Zero Patients met criteria&#xD;
  </why_stopped>
  <start_date type="Actual">December 19, 2019</start_date>
  <completion_date type="Anticipated">December 19, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 19, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Post-thrombotic syndrome at any time between 6-month and 24-month.</measure>
    <time_frame>6-24 months</time_frame>
    <description>Occurrence of post-thrombotic syndrome at any time between 6-month and 24-month after procedure by Villata score (Villata score &gt;5 or more), or if patient underwent an unplanned endovascular procedure to treat venous symptoms.&#xD;
The variables in villata scores are pain, cramps, heaviness, parasthesia, pruritus, pretibial edema, skin induration, hyperpigmentation, pain during calf compression, venous ectasia and redness.&#xD;
The Villata score ranges 0-45. Villata score &lt;5 means no post-thrombotic syndrome. Villata score 5-9 mild post-thrombotic syndrome. Villata score 10-14 means moderate post-thrombotic syndrome. Villata score ≥15 or presence of an ulcer indicates severe post-thrombotic syndrome.&#xD;
The more is the score the worse is the disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Post-thrombotic syndrome at 6 months.</measure>
    <time_frame>6 months</time_frame>
    <description>Occurrence of post-thrombotic syndrome at 6 months measured by Villata score (Villalta score was 5 or higher).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-thrombotic syndrome at 12 months.</measure>
    <time_frame>12 months</time_frame>
    <description>Occurrence of post-thrombotic syndrome at 12 months measured by Villata score (Villalta score was 5 or higher).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-thrombotic syndrome at 18 months.</measure>
    <time_frame>18 months</time_frame>
    <description>Occurrence of post-thrombotic syndrome at 18 months measured by Villata score (Villalta score was 5 or higher).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-thrombotic syndrome at 24 months.</measure>
    <time_frame>24 months</time_frame>
    <description>Occurrence of post-thrombotic syndrome at 24 months measured by Villata score (Villalta score was 5 or higher).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Villalta scale at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>The severity of the post-thrombotic syndrome to be evaluated at 6 months with the use of the Villalta scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Villalta scale at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>The severity of the post-thrombotic syndrome to be evaluated at 12 months with the use of the Villalta scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Villalta scale at 18 months</measure>
    <time_frame>18 months</time_frame>
    <description>The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Villalta scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Villalta scale at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Villalta scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Venous Clinical Severity Score at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>The severity of the post-thrombotic syndrome to be evaluated at 6 months with the use of the Venous Clinical Severity Score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Venous Clinical Severity Score at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>The severity of the post-thrombotic syndrome to be evaluated at 12 months with the use of the Venous Clinical Severity Score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Venous Clinical Severity Score at 18 months</measure>
    <time_frame>18 months</time_frame>
    <description>The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Venous Clinical Severity Score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Venous Clinical Severity Score at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>The severity of the post-thrombotic syndrome to be evaluated at 24 months with the use of the Venous Clinical Severity Score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life AT 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 12 months.</measure>
    <time_frame>12 months</time_frame>
    <description>Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 18 months.</measure>
    <time_frame>18 months</time_frame>
    <description>Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 18 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 24 months.</measure>
    <time_frame>24 months</time_frame>
    <description>Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 24 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 6 months.</measure>
    <time_frame>6 months</time_frame>
    <description>Health-Related Quality of Life measured by Generic Quality of Life at 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 12 months.</measure>
    <time_frame>12 months</time_frame>
    <description>Health-Related Quality of Life measured by Generic Quality of Life at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 18 months.</measure>
    <time_frame>18 months</time_frame>
    <description>Health-Related Quality of Life measured by Generic Quality of Life at 18 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 24 months.</measure>
    <time_frame>24 months</time_frame>
    <description>Health-Related Quality of Life measured by Generic Quality of Life at 24 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 6 months.</measure>
    <time_frame>6 months</time_frame>
    <description>Health-Related Quality of Life measured by Administration of QOL Measures at 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 12 months.</measure>
    <time_frame>12 months</time_frame>
    <description>Health-Related Quality of Life measured by Administration of QOL Measures at 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 18 months.</measure>
    <time_frame>18 months</time_frame>
    <description>Health-Related Quality of Life measured by Administration of QOL Measures at 18 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life at 24 months.</measure>
    <time_frame>24 months</time_frame>
    <description>Health-Related Quality of Life measured by Administration of QOL Measures at 24 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Failures that are Not PTS.</measure>
    <time_frame>6-24 months</time_frame>
    <description>Treatment Failures that are Not PTS (defined as one or more of the following during the 24 months post randomization: 1) the patient underwent an unplanned endovascular or surgical intervention for the treatment of severe symptomatic venous disease in the index leg within the first 24 months after randomization (2) the subject underwent an amputation in the index leg anytime within 24 months after randomization; or (3) the subject developed venous gangrene in the index leg within the first 24 months after randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of presenting DVT Symptoms at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of presenting DVT Symptoms at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of presenting DVT Symptoms at 18 months</measure>
    <time_frame>18 months</time_frame>
    <description>Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 18 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of presenting DVT Symptoms at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of presenting DVT Symptoms at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of presenting DVT Symptoms at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of presenting DVT Symptoms at 18 months</measure>
    <time_frame>18 months</time_frame>
    <description>Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 18 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of presenting DVT Symptoms at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Resolution of Thrombus with PCDT at 6 months.</measure>
    <time_frame>6 months</time_frame>
    <description>Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Resolution of Thrombus with PCDT at 12 months.</measure>
    <time_frame>12 months</time_frame>
    <description>Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Resolution of Thrombus with PCDT at 18 months.</measure>
    <time_frame>18 months</time_frame>
    <description>Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Resolution of Thrombus with PCDT at 24 months.</measure>
    <time_frame>24 months</time_frame>
    <description>Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Deep Venous Thrombosis</condition>
  <condition>Post Thrombotic Syndrome</condition>
  <arm_group>
    <arm_group_label>Pharmacomechanical thrombolysis plus anticoagulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group of patients will receive Pharmacomechanical catheter-directed thrombolysis (PCDT) plus Anticoagulation.&#xD;
PCDT will be AngioJet along with alteplase. Anticoagulation will be heparin only</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anticoagulation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This group of patients will receive standard anticoagulation only. Anticoagulation will be Heparin only</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Catheter directed thrombolysis plus anticoagulation</intervention_name>
    <description>Patients will be randomized to pharmacomechanical catheter directed thrombolysis plus anticoagulation.&#xD;
PCDT will be AngioJet along with alteplase.</description>
    <arm_group_label>Pharmacomechanical thrombolysis plus anticoagulation</arm_group_label>
    <other_name>Pharmacomechanical thrombolysis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anticoagulation</intervention_name>
    <description>Patients will receive anticoagulation alone. Anticoagulation will be heparin only.</description>
    <arm_group_label>Anticoagulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age&gt;18 and younger than 75&#xD;
&#xD;
          2. Symptomatic, proximal deep-vein thrombosis involving the Iliofemoral vein from&#xD;
             12/01/2019 to 12/01/2022&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age less than 18 years or greater than 75 years.&#xD;
&#xD;
          2. Symptom duration &gt; 14 days for the DVT episode in the index leg (i.e. non-acute DVT).&#xD;
&#xD;
          3. In the index leg: established PTS, or previous symptomatic DVT within the last 2&#xD;
             years.&#xD;
&#xD;
          4. In the contralateral (non-index) leg: symptomatic acute DVT a) involving the popliteal&#xD;
             and/or tibial veins; or b) for which thrombolysis is planned as part of initial&#xD;
             therapy.&#xD;
&#xD;
          5. Limb-threatening circulatory compromise.&#xD;
&#xD;
          6. PE with hemodynamic compromise (i.e. hypotension).&#xD;
&#xD;
          7. Inability to tolerate PCDT procedure due to severe dyspnea or acute systemic illness.&#xD;
&#xD;
          8. Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated&#xD;
             contrast, except for mild-moderate contrast allergies for which steroid pre-medication&#xD;
             can be used.&#xD;
&#xD;
          9. Hemoglobin &lt; 9.0 mg/dl, INR &gt; 1.6 before warfarin was started, or platelets &lt; 100,000&#xD;
             /ml.&#xD;
&#xD;
         10. Moderate renal impairment in diabetic patients (estimated GFR &lt; 60 ml/min) or severe&#xD;
             renal impairment in non-diabetic patients (estimated GFR &lt; 30 ml/min).&#xD;
&#xD;
         11. Active bleeding, recent (&lt; 3 months) GI bleeding, severe liver dysfunction, bleeding&#xD;
             diathesis.&#xD;
&#xD;
         12. Recent (&lt; 3 months) internal eye surgery or hemorrhagic retinopathy; recent (&lt; 10&#xD;
             days) major surgery, cataract surgery, trauma, CPR, obstetrical delivery, or other&#xD;
             invasive procedure.&#xD;
&#xD;
         13. History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation,&#xD;
             aneurysm.&#xD;
&#xD;
         14. Active cancer (metastatic, progressive, or treated within the last 6 months).&#xD;
             Exception: patients with non-melanoma primary skin cancers are eligible to participate&#xD;
             in the study.&#xD;
&#xD;
         15. Severe hypertension on repeated readings (systolic &gt; 180mmHg or diastolic &gt; 105 mmHg).&#xD;
&#xD;
         16. Pregnant (positive pregnancy test, women of childbearing potential must be tested).&#xD;
&#xD;
         17. Recently (&lt; 2 years or chronic non-ambulatory status.&#xD;
&#xD;
         18. Use of a thienopryridine antiplatelet drug (except clopidogrel) in the last 5 days.&#xD;
&#xD;
         19. Life expectancy &lt; 2 years or chronic non-ambulatory status.&#xD;
&#xD;
         20. Inability to provide informed consent or to comply with study assessments (e.g. due to&#xD;
             cognitive impairment or geographic distance).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ehab A Eltahawy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Toledo Health Science Campus</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Toledo Medical Center</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.gov/ct2/show/NCT00970619</url>
    <description>DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT. (NL28394)</description>
  </link>
  <reference>
    <citation>Vedantham S. Valvular dysfunction and venous obstruction in the post-thrombotic syndrome. Thromb Res. 2009;123 Suppl 4:S62-5. doi: 10.1016/S0049-3848(09)70146-X.</citation>
    <PMID>19303507</PMID>
  </reference>
  <reference>
    <citation>DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT. Clinicaltrial.gov</citation>
  </reference>
  <results_reference>
    <citation>Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis. 2009 Nov;28(4):465-76. doi: 10.1007/s11239-009-0309-3. Epub 2009 Feb 18.</citation>
    <PMID>19224134</PMID>
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  <results_reference>
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    <PMID>19017588</PMID>
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  <results_reference>
    <citation>Kahn SR, Comerota AJ, Cushman M, Evans NS, Ginsberg JS, Goldenberg NA, Gupta DK, Prandoni P, Vedantham S, Walsh ME, Weitz JI; American Heart Association Council on Peripheral Vascular Disease, Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014 Oct 28;130(18):1636-61. doi: 10.1161/CIR.0000000000000130. Epub 2014 Sep 22. No abstract available. Erratum In: Circulation. 2015 Feb 24;131(8):e359.</citation>
    <PMID>25246013</PMID>
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  <results_reference>
    <citation>Comerota AJ, Grewal N, Martinez JT, Chen JT, Disalle R, Andrews L, Sepanski D, Assi Z. Postthrombotic morbidity correlates with residual thrombus following catheter-directed thrombolysis for iliofemoral deep vein thrombosis. J Vasc Surg. 2012 Mar;55(3):768-73. doi: 10.1016/j.jvs.2011.10.032. Epub 2012 Jan 24. Erratum In: J Vasc Surg. 2012 May;55(5):1547.</citation>
    <PMID>22277690</PMID>
  </results_reference>
  <results_reference>
    <citation>Schweizer J, Kirch W, Koch R, Elix H, Hellner G, Forkmann L, Graf A. Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol. 2000 Oct;36(4):1336-43. doi: 10.1016/s0735-1097(00)00863-9.</citation>
    <PMID>11028492</PMID>
  </results_reference>
  <results_reference>
    <citation>Goldhaber SZ, Buring JE, Lipnick RJ, Hennekens CH. Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis. Am J Med. 1984 Mar;76(3):393-7. doi: 10.1016/0002-9343(84)90656-9.</citation>
    <PMID>6367454</PMID>
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  <results_reference>
    <citation>Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg. 2002 Sep;24(3):209-14. doi: 10.1053/ejvs.2002.1665.</citation>
    <PMID>12217281</PMID>
  </results_reference>
  <results_reference>
    <citation>Bashir R, Zack CJ, Zhao H, Comerota AJ, Bove AA. Comparative outcomes of catheter-directed thrombolysis plus anticoagulation vs anticoagulation alone to treat lower-extremity proximal deep vein thrombosis. JAMA Intern Med. 2014 Sep;174(9):1494-501. doi: 10.1001/jamainternmed.2014.3415.</citation>
    <PMID>25047081</PMID>
  </results_reference>
  <results_reference>
    <citation>Enden T, Haig Y, Klow NE, Slagsvold CE, Sandvik L, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbaek G, Sandset PM; CaVenT Study Group. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012 Jan 7;379(9810):31-8. doi: 10.1016/S0140-6736(11)61753-4. Epub 2011 Dec 13.</citation>
    <PMID>22172244</PMID>
  </results_reference>
  <results_reference>
    <citation>Haig Y, Enden T, Grotta O, Klow NE, Slagsvold CE, Ghanima W, Sandvik L, Hafsahl G, Holme PA, Holmen LO, Njaaastad AM, Sandbaek G, Sandset PM; CaVenT Study Group. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016 Feb;3(2):e64-71. doi: 10.1016/S2352-3026(15)00248-3. Epub 2016 Jan 6.</citation>
    <PMID>26853645</PMID>
  </results_reference>
  <results_reference>
    <citation>Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, Magnuson E, Razavi MK, Comerota AJ, Gornik HL, Murphy TP, Lewis L, Duncan JR, Nieters P, Derfler MC, Filion M, Gu CS, Kee S, Schneider J, Saad N, Blinder M, Moll S, Sacks D, Lin J, Rundback J, Garcia M, Razdan R, VanderWoude E, Marques V, Kearon C; ATTRACT Trial Investigators. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med. 2017 Dec 7;377(23):2240-2252. doi: 10.1056/NEJMoa1615066.</citation>
    <PMID>29211671</PMID>
  </results_reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>May 7, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>September 1, 2021</last_update_submitted>
  <last_update_submitted_qc>September 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Toledo Health Science Campus</investigator_affiliation>
    <investigator_full_name>Ehab Eltahawy, MD</investigator_full_name>
    <investigator_title>Associate professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
    <mesh_term>Postthrombotic Syndrome</mesh_term>
    <mesh_term>Postphlebitic Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04411316
org study id: 300439
nct id: NCT04411316
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: Yes
is us export: Yes
Post-thrombotic syndrome (PTS) is a complication that can develop after deep vein thrombosis
      (DVT) of the lower extremities. PTS can occur at various times after the initial episode, but
      usually manifests within two years of initial DVT onset. Early and more complete thrombus
      clearance is believed by many to relieve venous outflow obstruction, preserve valvular
      function and reduce venous hypertension. Two previously published randomized controlled
      trials, the CAVENT trial and the ATTRACT trial, were larger and designed to investigate the
      efficacy of CDT. However, both of these trials included patients with iliofemoral as well as
      femoro-popliteal deep vein thrombosis. Our study will be limited to patients with iliofemoral
      deep vein thrombosis to assess whether Pharmacomechanical catheter-directed thrombolysis
      (PCDT) therapy utilizing AngioJet and tPA can safely and effectively reduce post thrombotic
      syndrome after 24 months.
Patients with Iliofemoral DVT are theoretically at the highest risk for development of PRS
      given involvement of the major drainage pathway of both superficial femoral and deep femoral
      veins. This would not only affect the primary venous drainage, but would also compromise the
      ability to develop efficient collateral pathways. This creates higher chances of developing
      post-thrombotic syndrome (PTS). The proposed trial would utilize Angiojet thrombectomy
      followed by catheter directed thrombolysis and Anticoagulation compared to Anticoagulation
      alone. To assess whether Pharmacomechanical catheter-directed thrombolysis (PCDT) therapy
      utilizing AngioJet and tPA for the treatment of iliofemoral deep venous thrombosis can safely
      and effectively reduce post thrombotic syndrome after 24 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Post-thrombotic syndrome at any time between 6-month and 24-month.
time frame: 6-24 months
description: Occurrence of post-thrombotic syndrome at any time between 6-month and 24-month after procedure by Villata score (Villata score >5 or more), or if patient underwent an unplanned endovascular procedure to treat venous symptoms.
The variables in villata scores are pain, cramps, heaviness, parasthesia, pruritus, pretibial edema, skin induration, hyperpigmentation, pain during calf compression, venous ectasia and redness.
The Villata score ranges 0-45. Villata score <5 means no post-thrombotic syndrome. Villata score 5-9 mild post-thrombotic syndrome. Villata score 10-14 means moderate post-thrombotic syndrome. Villata score ≥15 or presence of an ulcer indicates severe post-thrombotic syndrome.
The more is the score the worse is the disease.
measure: Post-thrombotic syndrome at 6 months.
time frame: 6 months
description: Occurrence of post-thrombotic syndrome at 6 months measured by Villata score (Villalta score was 5 or higher).
measure: Post-thrombotic syndrome at 12 months.
time frame: 12 months
description: Occurrence of post-thrombotic syndrome at 12 months measured by Villata score (Villalta score was 5 or higher).
measure: Post-thrombotic syndrome at 18 months.
time frame: 18 months
description: Occurrence of post-thrombotic syndrome at 18 months measured by Villata score (Villalta score was 5 or higher).
measure: Post-thrombotic syndrome at 24 months.
time frame: 24 months
description: Occurrence of post-thrombotic syndrome at 24 months measured by Villata score (Villalta score was 5 or higher).
measure: Villalta scale at 6 months
time frame: 6 months
description: The severity of the post-thrombotic syndrome to be evaluated at 6 months with the use of the Villalta scale
measure: Villalta scale at 12 months
time frame: 12 months
description: The severity of the post-thrombotic syndrome to be evaluated at 12 months with the use of the Villalta scale.
measure: Villalta scale at 18 months
time frame: 18 months
description: The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Villalta scale.
measure: Villalta scale at 24 months
time frame: 24 months
description: The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Villalta scale.
measure: Venous Clinical Severity Score at 6 months
time frame: 6 months
description: The severity of the post-thrombotic syndrome to be evaluated at 6 months with the use of the Venous Clinical Severity Score.
measure: Venous Clinical Severity Score at 12 months
time frame: 12 months
description: The severity of the post-thrombotic syndrome to be evaluated at 12 months with the use of the Venous Clinical Severity Score.
measure: Venous Clinical Severity Score at 18 months
time frame: 18 months
description: The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Venous Clinical Severity Score.
measure: Venous Clinical Severity Score at 24 months
time frame: 24 months
description: The severity of the post-thrombotic syndrome to be evaluated at 24 months with the use of the Venous Clinical Severity Score.
measure: Health-Related Quality of Life AT 6 months
time frame: 6 months
description: Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life
measure: Health-Related Quality of Life at 12 months.
time frame: 12 months
description: Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 12 months.
measure: Health-Related Quality of Life at 18 months.
time frame: 18 months
description: Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 18 months.
measure: Health-Related Quality of Life at 24 months.
time frame: 24 months
description: Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 24 months.
measure: Health-Related Quality of Life at 6 months.
time frame: 6 months
description: Health-Related Quality of Life measured by Generic Quality of Life at 6 months.
measure: Health-Related Quality of Life at 12 months.
time frame: 12 months
description: Health-Related Quality of Life measured by Generic Quality of Life at 12 months
measure: Health-Related Quality of Life at 18 months.
time frame: 18 months
description: Health-Related Quality of Life measured by Generic Quality of Life at 18 months.
measure: Health-Related Quality of Life at 24 months.
time frame: 24 months
description: Health-Related Quality of Life measured by Generic Quality of Life at 24 months.
measure: Health-Related Quality of Life at 6 months.
time frame: 6 months
description: Health-Related Quality of Life measured by Administration of QOL Measures at 6 months.
measure: Health-Related Quality of Life at 12 months.
time frame: 12 months
description: Health-Related Quality of Life measured by Administration of QOL Measures at 12 months.
measure: Health-Related Quality of Life at 18 months.
time frame: 18 months
description: Health-Related Quality of Life measured by Administration of QOL Measures at 18 months.
measure: Health-Related Quality of Life at 24 months.
time frame: 24 months
description: Health-Related Quality of Life measured by Administration of QOL Measures at 24 months.
measure: Treatment Failures that are Not PTS.
time frame: 6-24 months
description: Treatment Failures that are Not PTS (defined as one or more of the following during the 24 months post randomization: 1) the patient underwent an unplanned endovascular or surgical intervention for the treatment of severe symptomatic venous disease in the index leg within the first 24 months after randomization (2) the subject underwent an amputation in the index leg anytime within 24 months after randomization; or (3) the subject developed venous gangrene in the index leg within the first 24 months after randomization.
measure: Severity of presenting DVT Symptoms at 6 months
time frame: 6 months
description: Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 6 months
measure: Severity of presenting DVT Symptoms at 12 months
time frame: 12 months
description: Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 12 months
measure: Severity of presenting DVT Symptoms at 18 months
time frame: 18 months
description: Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 18 months
measure: Severity of presenting DVT Symptoms at 24 months
time frame: 24 months
description: Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 24 months
measure: Severity of presenting DVT Symptoms at 6 months
time frame: 6 months
description: Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 6 months
measure: Severity of presenting DVT Symptoms at 12 months
time frame: 12 months
description: Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 12 months
measure: Severity of presenting DVT Symptoms at 18 months
time frame: 18 months
description: Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 18 months
measure: Severity of presenting DVT Symptoms at 24 months
time frame: 24 months
description: Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 24 months
measure: Degree of Resolution of Thrombus with PCDT at 6 months.
time frame: 6 months
description: Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.
measure: Degree of Resolution of Thrombus with PCDT at 12 months.
time frame: 12 months
description: Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.
measure: Degree of Resolution of Thrombus with PCDT at 18 months.
time frame: 18 months
description: Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.
measure: Degree of Resolution of Thrombus with PCDT at 24 months.
time frame: 24 months
description: Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.
arm group label: Pharmacomechanical thrombolysis plus anticoagulation
arm group type: Experimental
description: This group of patients will receive Pharmacomechanical catheter-directed thrombolysis (PCDT) plus Anticoagulation.
PCDT will be AngioJet along with alteplase. Anticoagulation will be heparin only
arm group label: Anticoagulation
arm group type: Active Comparator
description: This group of patients will receive standard anticoagulation only. Anticoagulation will be Heparin only
intervention type: Combination Product
intervention name: Catheter directed thrombolysis plus anticoagulation
description: Patients will be randomized to pharmacomechanical catheter directed thrombolysis plus anticoagulation.
PCDT will be AngioJet along with alteplase.
arm group label: Pharmacomechanical thrombolysis plus anticoagulation
other name: Pharmacomechanical thrombolysis
intervention type: Drug
intervention name: Anticoagulation
description: Patients will receive anticoagulation alone. Anticoagulation will be heparin only.
arm group label: Anticoagulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ehab A Eltahawy, MD
role: Principal Investigator
affiliation: University of Toledo Health Science Campus
facility: 
country: United States
url: https://clinicaltrials.gov/ct2/show/NCT00970619
description: DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT. (NL28394)
citation: Vedantham S. Valvular dysfunction and venous obstruction in the post-thrombotic syndrome. Thromb Res. 2009;123 Suppl 4:S62-5. doi: 10.1016/S0049-3848(09)70146-X.
PMID: 19303507
citation: DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT. Clinicaltrial.gov
citation: Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis. 2009 Nov;28(4):465-76. doi: 10.1007/s11239-009-0309-3. Epub 2009 Feb 18.
PMID: 19224134
citation: Kahn SR, Shrier I, Julian JA, Ducruet T, Arsenault L, Miron MJ, Roussin A, Desmarais S, Joyal F, Kassis J, Solymoss S, Desjardins L, Lamping DL, Johri M, Ginsberg JS. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med. 2008 Nov 18;149(10):698-707. doi: 10.7326/0003-4819-149-10-200811180-00004.
PMID: 19017588
citation: Kahn SR, Comerota AJ, Cushman M, Evans NS, Ginsberg JS, Goldenberg NA, Gupta DK, Prandoni P, Vedantham S, Walsh ME, Weitz JI; American Heart Association Council on Peripheral Vascular Disease, Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014 Oct 28;130(18):1636-61. doi: 10.1161/CIR.0000000000000130. Epub 2014 Sep 22. No abstract available. Erratum In: Circulation. 2015 Feb 24;131(8):e359.
PMID: 25246013
citation: Comerota AJ, Grewal N, Martinez JT, Chen JT, Disalle R, Andrews L, Sepanski D, Assi Z. Postthrombotic morbidity correlates with residual thrombus following catheter-directed thrombolysis for iliofemoral deep vein thrombosis. J Vasc Surg. 2012 Mar;55(3):768-73. doi: 10.1016/j.jvs.2011.10.032. Epub 2012 Jan 24. Erratum In: J Vasc Surg. 2012 May;55(5):1547.
PMID: 22277690
citation: Schweizer J, Kirch W, Koch R, Elix H, Hellner G, Forkmann L, Graf A. Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol. 2000 Oct;36(4):1336-43. doi: 10.1016/s0735-1097(00)00863-9.
PMID: 11028492
citation: Goldhaber SZ, Buring JE, Lipnick RJ, Hennekens CH. Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis. Am J Med. 1984 Mar;76(3):393-7. doi: 10.1016/0002-9343(84)90656-9.
PMID: 6367454
citation: Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg. 2002 Sep;24(3):209-14. doi: 10.1053/ejvs.2002.1665.
PMID: 12217281
citation: Bashir R, Zack CJ, Zhao H, Comerota AJ, Bove AA. Comparative outcomes of catheter-directed thrombolysis plus anticoagulation vs anticoagulation alone to treat lower-extremity proximal deep vein thrombosis. JAMA Intern Med. 2014 Sep;174(9):1494-501. doi: 10.1001/jamainternmed.2014.3415.
PMID: 25047081
citation: Enden T, Haig Y, Klow NE, Slagsvold CE, Sandvik L, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbaek G, Sandset PM; CaVenT Study Group. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012 Jan 7;379(9810):31-8. doi: 10.1016/S0140-6736(11)61753-4. Epub 2011 Dec 13.
PMID: 22172244
citation: Haig Y, Enden T, Grotta O, Klow NE, Slagsvold CE, Ghanima W, Sandvik L, Hafsahl G, Holme PA, Holmen LO, Njaaastad AM, Sandbaek G, Sandset PM; CaVenT Study Group. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016 Feb;3(2):e64-71. doi: 10.1016/S2352-3026(15)00248-3. Epub 2016 Jan 6.
PMID: 26853645
citation: Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, Magnuson E, Razavi MK, Comerota AJ, Gornik HL, Murphy TP, Lewis L, Duncan JR, Nieters P, Derfler MC, Filion M, Gu CS, Kee S, Schneider J, Saad N, Blinder M, Moll S, Sacks D, Lin J, Rundback J, Garcia M, Razdan R, VanderWoude E, Marques V, Kearon C; ATTRACT Trial Investigators. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med. 2017 Dec 7;377(23):2240-2252. doi: 10.1056/NEJMoa1615066.
PMID: 29211671
responsible party type: Principal Investigator
investigator affiliation: University of Toledo Health Science Campus
investigator full name: Ehab Eltahawy, MD
investigator title: Associate professor of Medicine
mesh term: Thrombosis
mesh term: Venous Thrombosis
mesh term: Postthrombotic Syndrome
mesh term: Postphlebitic Syndrome
sharing ipd: No