Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis - Full Text View

Sponsors and Collaborators:	Washington University School of Medicine National Heart, Lung, and Blood Institute (NHLBI) Genentech Bacchus Vascular Possis Medical BSN-JOBST Inc.
Information provided by:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00790335

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 III

MedlinePlus related topics: Deep Vein Thrombosis

Drug Information available for: Alteplase Tissue-type plasminogen activator

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis--The ATTRACT Trial

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:	December 2008
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A-Intervention: Experimental 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.
B-Control: No Intervention 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

Arms

Assigned Interventions

A-Intervention: Experimental

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.

B-Control: No Intervention

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 70 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 70 years.
Symptom duration > 14 days for the current DVT episode (i.e. subacute or chronic DVT).
Established PTS in the ipsilateral leg, previous symptomatic DVT episode in the ipsilateral leg within the last 2 years, or recent (< 1 month) symptomatic DVT in the contralateral leg.
Presence of IVC filter with associated thrombus (acute or chronic), or DVT known to extend > 3 cm into the IVC (if a filter is present, the IVC should be imaged prior to randomization).
Limb-threatening circulatory compromise (i.e., phlegmasia cerulea dolens).
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).
Severe hypertension on repeated readings (systolic > 180 mmHg or diastolic > 105 mmHg).
Pregnant (positive pregnancy test, women of childbearing age must be tested).
Recently (< 1 mo) had thrombolysis or is participating in another investigational drug study.
Use of clopidogrel, ticlopidine, or other thienopyridine antiplatelet drug in the last 7 days.
Life expectancy < 2 years or chronic non-ambulatory status.
Inability to comply with study assessments (e.g. due to geographic distance).

Contacts and Locations

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

Locations

United States, Delaware
Christiana Care Health Systems
Newark, Delaware, United States, 19718
United States, District of Columbia
Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Illinois
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
Ann Arbor Veteran's Administration Health System
Ann Arbor, Michigan, United States, 48105
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New Jersey
Holy Name Hospital
Teaneck, New Jersey, United States, 07666
United States, New York
Mount Sinai Medical Center
New York City, New York, United States, 10029
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Jobst Vascular Center
Toledo, Ohio, United States, 43606
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, South Carolina
Greenville Hospital System
Greenville, South Carolina, United States, 29615
United States, Utah
Utah Valley Regional Medical Center
Provo, Utah, United States, 84604
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
United States, Washington
Sacred Heart Medical Center
Spokane, Washington, United States, 99204

Sponsors and Collaborators

Washington University School of Medicine

National Heart, Lung, and Blood Institute (NHLBI)

Genentech

Bacchus Vascular

Possis Medical

BSN-JOBST Inc.

Investigators

Principal Investigator:	Suresh Vedantham, MD	Washington University School of Medicine
Study Chair:	Samuel Z Goldhaber, MD	Brigham and Women's Hospital

More Information

The Long-Term Clinical Course of Acute Deep Vein Thrombosis This link exits the ClinicalTrials.gov site

Predictors of the Post Thrombotic Syndrome During Long-Term Treatment of Proximal Deep Vein Thrombosis This link exits the ClinicalTrials.gov site

Deep Vein Thrombosis This link exits the ClinicalTrials.gov site

Below-Knee Elastic Compression Stockings to Prevent the Post Thrombotic Syndrome This link exits the ClinicalTrials.gov site

Publications:

Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ; American College of Chest Physicians. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):454S-545S. Erratum in: Chest. 2008 Oct;134(4):892.

Kahn SR. The post-thrombotic syndrome: the forgotten morbidity of deep venous thrombosis. J Thromb Thrombolysis. 2006 Feb;21(1):41-8. Review.

Vedantham S, Millward SF, Cardella JF, Hofmann LV, Razavi MK, Grassi CJ, Sacks D, Kinney TB; Society of Interventional Radiology. Society of Interventional Radiology position statement: treatment of acute iliofemoral deep vein thrombosis with use of adjunctive catheter-directed intrathrombus thrombolysis. J Vasc Interv Radiol. 2006 Apr;17(4):613-6. No abstract available.

Vedantham S, Vesely TM, Sicard GA, Brown D, Rubin B, Sanchez LA, Parti N, Picus D. Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein thrombosis. J Vasc Interv Radiol. 2004 Jun;15(6):565-74.

Responsible Party:	Washington University School of Medicine ( Suresh Vedantham, M.D. )
Study ID Numbers:	22326953211, U01 HL088476-01A1
Study First Received:	October 15, 2008
Last Updated:	November 12, 2008
ClinicalTrials.gov Identifier:	NCT00790335
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

Study placed in the following topic categories:

Peripheral Vascular Diseases
Vascular Diseases
Tissue Plasminogen Activator
Postthrombotic Syndrome
Venous Thromboembolism
Thrombosis
Thromboembolism

Embolism and Thrombosis
Embolism
Venous Insufficiency
Phlebitis
Venous Thrombosis
Plasminogen
Postphlebitic Syndrome

Additional relevant MeSH terms:

Fibrin Modulating Agents
Pathologic Processes
Disease
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Syndrome

Hematologic Agents
Fibrinolytic Agents
Cardiovascular Diseases
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009