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Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT)

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ClinicalTrials.gov Identifier: NCT00790335
Recruitment Status : Completed
First Posted : November 13, 2008
Results First Posted : March 29, 2018
Last Update Posted : March 29, 2018
Sponsor:
Collaborators:
McMaster University
Ontario Clinical Oncology Group (OCOG)
National Heart, Lung, and Blood Institute (NHLBI)
BSN Medical Inc
Genentech, Inc.
Medtronic - MITG
Boston Scientific Corporation
Mid America Heart Institute
Society of Interventional Radiology Foundation
Massachusetts General Hospital
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The purpose of this study is to determine if the use of adjunctive Pharmacomechanical Catheter Directed Thrombolysis, which includes the intrathrombus administration of rt-PA--Activase (Alteplase),can prevent the post-thrombotic syndrome(PTS)in patients with symptomatic proximal deep vein thrombosis(DVT)as compared with optimal standard DVT therapy alone.

Condition or disease Intervention/treatment Phase
Deep Vein Thrombosis Venous Thrombosis Postphlebitic Syndrome Venous Thromboembolism Post Thrombotic Syndrome Drug: Recombinant tissue plasminogen activator (rt-PA) Phase 3

Detailed Description:

Activase, 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 established 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 the post-thrombotic syndrome (PTS), a morbid, late complication of DVT that occurs in nearly 50% of patients.

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, pharmacomechanical catheter-directed intrathrombus thrombolysis (PCDT),is thought to be safer, more effective, and more efficient than previous methods. The question of whether PCDT using rt-PA improves long-term DVT patient outcomes with acceptable risk and cost has not yet been addressed.

The rationale for performing the ATTRACT Trial is based upon:

  • the major burden of PTS on DVT patients and the U.S. healthcare system
  • the association between rapid clot lysis and prevention of PTS
  • the proven ability of rt-PA to dissolve venous thrombus in proximal DVT
  • recent advances in CDT methods which may lower bleeding risk
  • the major clinical controversy on whether CDT should be routinely used for first-line DVT therapy

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 692 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis--The ATTRACT Trial
Study Start Date : November 2009
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Alteplase

Arm Intervention/treatment
Experimental: A-Intervention
PCDT with intrathrombus delivery of recombinant tissue plasminogen activator (rt-PA, maximum allowable total dose 35 mg) into the DVT over a period of up to 24 hours. Three methods of initial rt-PA delivery will be used: 1) Trellis-8 Peripheral Infusion System - maximum first-session rt-PA dose 25 mg; 2) AngioJet Rheolytic Thrombectomy System - maximum first-session rt-PA dose 25 mg; or 3) Catheter-directed rt-PA infusion for up to 24 hours at 0.01 mg/kg/hr (maximum 1.0 mg/hr) via a multisidehole infusion catheter. Before and after PCDT, patients will receive standard DVT therapy as in the Control Arm
Drug: Recombinant tissue plasminogen activator (rt-PA)
Pharmacomechanical catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.
Other Names:
  • rt-PA
  • recombinant tissue plasminogen activator
  • Activase
  • Alteplase

No Intervention: B-Control
Initial anticoagulant therapy with unfractionated heparin, enoxaparin, dalteparin, or tinzaparin, for at least 5 days, overlapped with long-term oral warfarin (target international normalized ratio 2.0 - 3.0). Elastic compression stockings will be prescribed



Primary Outcome Measures :
  1. Cumulative Incidence of Post-Thrombotic Syndrome (Villalta Scale) [ Time Frame: Between 6 and 24 months after randomization ]
    Patients who experienced one of the following occurrences in the index leg between the 6 month and 24 month post-randomization follow-up visits, inclusive: 1) Villalta score of 5 or greater; 2) leg ulcer; or 3) late endovascular procedure performed to treat severe venous disease. The Villalta scale ranges from 0-33 points, with higher scores being worse.


Secondary Outcome Measures :
  1. Major Non-post-thrombotic Syndrome Treatment Failure [ Time Frame: Through 24 months ]
    A major non-post-thrombotic-syndrome treatment failure refers to when any of three events occurred in the index leg: 1) an unplanned endovascular procedure to treat severe venous symptoms within 6 months post-randomization; 2) venous gangrene within 6 months; or 3) an amputation within 24 months.

  2. Any Treatment Failure [ Time Frame: Through 24 months ]
    Composite of PTS and major non-PTS treatment failure

  3. Moderate-to-severe Post-thrombotic Syndrome [ Time Frame: Between 6 and 24 months after randomization ]
    Proportion of patients with Villalta score of 10 or higher at any time between the 6 month and 24 month follow-up visits, inclusive. The Villalta scale ranges from 0-33 points, with higher scores being worse.

  4. Major Bleeding [ Time Frame: Within 10 days after randomization ]
    Defined as clinically overt bleeding that is associated with a fall in the hemoglobin level of at least 2.0 g/dl, transfusion of ≥ 2 units of red blood cells, or involvement of a critical site (e.g. intracranial, intraspinal).

  5. Major Bleeding [ Time Frame: Within 24 months after randomization ]
    Defined as clinically overt bleeding that was associated with a fall in the hemoglobin level of at least 2.0 g/dl, transfusion of ≥ 2 units of red blood cells, or involvement of a critical site (e.g. intracranial, intraspinal).

  6. Any (Minor + Major) Bleeding [ Time Frame: Within 10 days after randomization ]
    Clinically overt bleeding that occurred through 10 days post-randomization

  7. Any (Major + Minor) Bleeding [ Time Frame: Within 24 months after randomization ]
    Clinically overt bleeding that occurred within 24 months post-randomization

  8. Recurrent Venous Thromboembolism [ Time Frame: Within 10 days after randomization ]
    Proportion of patients with symptomatic recurrent venous thromboembolism (including DVT and/or PE)

  9. Recurrent Venous Thromboembolism [ Time Frame: Within 24 months after randomization ]
    Symptomatic recurrent venous thromboembolism (DVT and/or PE)

  10. Death [ Time Frame: Within 10 days after randomization ]
    All-cause mortality

  11. Death [ Time Frame: Within 24 months after randomization ]
    All-cause mortality

  12. Severity of Post-thrombotic Syndrome (Villalta) [ Time Frame: At 6 months ]
    Mean Villalta scale score at the specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.

  13. Severity of Post-thrombotic Syndrome (Villalta) [ Time Frame: At 12 months ]
    Mean Villalta scale score at the specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.

  14. Severity of Post-thrombotic Syndrome (Villalta) [ Time Frame: At 18 months ]
    Mean Villalta scale score at specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.

  15. Severity of Post-thrombotic Syndrome (Villalta) [ Time Frame: At 24 months ]
    Mean Villalta scale score at specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.

  16. Venous Clinical Severity Score [ Time Frame: At 6 months ]
    Mean Venous Clinical Severity Score (VCSS) at the specified follow-up visit; range 0-27 (did not use compression item), higher score is worse

  17. Venous Clinical Severity Score [ Time Frame: At 12 months ]
    Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)

  18. Venous Clinical Severity Score [ Time Frame: At 18 months ]
    Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)

  19. Venous Clinical Severity Score [ Time Frame: At 24 months ]
    Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)

  20. Change in General Quality of Life - Physical [ Time Frame: Baseline to 24 months post-randomization ]
    Short-Form-36 Health Survey, Version 2, Physical Component Summary (PCS) Scale. Range of scores 0-100 with higher scores representing better quality of life.

  21. Change in General Quality of Life - Mental [ Time Frame: Baseline to 24 months post-randomization ]
    Short-Form-36 Health Survey, Version 2, Mental Component Summary (MCS) Scale. Range of scores 0-100 with higher scores representing better quality of life.

  22. Change in Venous Disease-specific Quality of Life [ Time Frame: Baseline to 24 months post-randomization ]
    Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) questionnaire. Range of scores 0-100 with higher scores representing better quality of life, and higher change scores representing greater improvement from baseline.

  23. Change in Leg Pain Severity [ Time Frame: Baseline to 10 days post-randomization ]
    Likert pain scale ranging from 1-7, with higher scores representing a greater intensity of pain

  24. Change in Leg Pain Severity [ Time Frame: Baseline to 30 days post-randomization ]
    Likert pain scale ranging from 1-7, with higher scores representing a greater intensity of pain

  25. Change in Leg Circumference [ Time Frame: Baseline to 10 days post-randomization ]
    Mean calf circumference measured 10 cm below the tibial tuberosity

  26. Change in Leg Circumference [ Time Frame: Baseline to 30 days post-randomization ]
    Mean calf circumference measured 10 cm below the tibial tuberosity



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Symptomatic proximal DVT involving the iliac, common femoral, and/or femoral vein.

Exclusion Criteria:

  • Age less than 16 years or greater than 75 years.
  • Symptom duration > 14 days for the DVT episode in the index leg (i.e., non-acute DVT).
  • In the index leg: established PTS, or previous symptomatic DVT within the last 2 years.
  • In the contralateral (non-index) leg: symptomatic acute DVT a) involving the iliac and/or common femoral vein; or b) for which thrombolysis is planned as part of the initial therapy.
  • Limb-threatening circulatory compromise.
  • Pulmonary embolism with hemodynamic compromise (i.e., hypotension).
  • Inability to tolerate PCDT procedure due to severe dyspnea or acute systemic illness.
  • Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
  • Hemoglobin < 9.0 mg/dl, INR > 1.6 before warfarin was started, or platelets < 100,000/ml.
  • Moderate renal impairment in diabetic patients (estimated glomerular filtration rate [GFR] < 60 ml/min) or severe renal impairment in non-diabetic patients (estimated GFR < 30 ml/min).
  • Active bleeding, recent (< 3 mo) GI bleeding, severe liver dysfunction, bleeding diathesis.
  • Recent (< 3 mo) internal eye surgery or hemorrhagic retinopathy; recent (< 10 days) major surgery, cataract surgery, trauma, cardiopulmonary resuscitation, obstetrical delivery, or other invasive procedure.
  • History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation, aneurysm.
  • Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: patients with non-melanoma primary skin cancers are eligible to participate in the study.
  • Severe hypertension on repeated readings (systolic > 180 mmHg or diastolic > 105 mmHg).
  • Pregnant (positive pregnancy test, women of childbearing potential must be tested).
  • Recently (< 1 mo) had thrombolysis or is participating in another investigational drug study.
  • Use of a thienopyridine antiplatelet drug (except clopidogrel) in the last 5 days.
  • Life expectancy < 2 years or chronic non-ambulatory status.
  • Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance).

Information from the National Library of Medicine

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): NCT00790335


  Show 56 Study Locations
Sponsors and Collaborators
Washington University School of Medicine
McMaster University
Ontario Clinical Oncology Group (OCOG)
National Heart, Lung, and Blood Institute (NHLBI)
BSN Medical Inc
Genentech, Inc.
Medtronic - MITG
Boston Scientific Corporation
Mid America Heart Institute
Society of Interventional Radiology Foundation
Massachusetts General Hospital
Investigators
Principal Investigator: Suresh Vedantham, M.D. Clinical Coordinating Center at Washington University School of Medicine
Principal Investigator: Clive Kearon, MB, MRCP, FRCP(C), PhD Data Coordinating Center at McMaster University-Ontario Clinical Oncology Group
Study Chair: Samuel Z Goldhaber, M.D. Brigham and Women's Hospital

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00790335     History of Changes
Other Study ID Numbers: 22326953211
U01HL088476-01A1 ( U.S. NIH Grant/Contract )
First Posted: November 13, 2008    Key Record Dates
Results First Posted: March 29, 2018
Last Update Posted: March 29, 2018
Last Verified: February 2018

Keywords provided by Washington University School of Medicine:
ATTRACT
deep vein thrombosis
deep venous thrombosis
post thrombotic syndrome
blood clot
thrombolysis
tissue plasminogen activator
rt-PA
Activase
mechanical thrombectomy
pharmacomechanical

Additional relevant MeSH terms:
Syndrome
Thrombosis
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Postthrombotic Syndrome
Postphlebitic Syndrome
Disease
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Venous Insufficiency
Phlebitis
Peripheral Vascular Diseases
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action