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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Washington University School of Medicine
Sponsor:
Collaborators:
McMaster University
Ontario Clinical Oncology Group (OCOG)
BSN Medical Inc
Genentech
Covidien
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
ClinicalTrials.gov Identifier:
NCT00790335
First received: October 15, 2008
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis--The ATTRACT Trial

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Cumulative incidence of Post-Thrombotic Syndrome (Villalta Scale) [ Time Frame: within 24 months after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Severity of post thrombotic syndrome, resolution of presenting DVT symptoms, the prevalence of valvular reflux and residual thrombus, the degree of clot lysis, and cost-effectiveness. [ Time Frame: within 24 months of randomization ] [ Designated as safety issue: No ]
  • Major bleeding, symptomatic pulmonary embolism, recurrent venous thromboembolism, and death [ Time Frame: within 10 days and 24 months after randomization ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 692
Study Start Date: November 2009
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A-Intervention
PCDT with intrathrombus delivery of 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 INR 2.0 - 3.0). Elastic compression stockings will be prescribed

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
  Eligibility

Ages Eligible for Study:   16 Years to 75 Years
Genders Eligible for Study:   Both
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.
  • PE 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 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, CPR, 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790335

Contacts
Contact: Patty M Nieters, RN, BSN 314 362 3371 nietersp@mir.wustl.edu

  Show 58 Study Locations
Sponsors and Collaborators
Washington University School of Medicine
McMaster University
Ontario Clinical Oncology Group (OCOG)
BSN Medical Inc
Genentech
Covidien
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
  More Information

Additional Information:
Publications:
Additional 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, U01 HL088476-01A1
Study First Received: October 15, 2008
Last Updated: September 22, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 01, 2014