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

Sponsor:	Washington University School of Medicine
Collaborators:	McMaster University Ontario Clinical Oncology Group (OCOG) National Heart, Lung, and Blood Institute (NHLBI) Bacchus Vascular BSN Medical Inc Genentech MEDRAD Interventional/Possis 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

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:

MedlinePlus related topics: Blood Thinners Deep Vein Thrombosis

U.S. FDA Resources

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:	January 2015
Estimated Primary Completion Date:	January 2015 (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

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 thienopryridine 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

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 54 Study Locations

Sponsors and Collaborators

Washington University School of Medicine

McMaster University

Ontario Clinical Oncology Group (OCOG)

National Heart, Lung, and Blood Institute (NHLBI)

Bacchus Vascular

BSN Medical Inc

Genentech

MEDRAD Interventional/Possis

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:

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Comerota AJ. The ATTRACT trial: rationale for early intervention for iliofemoral DVT. Perspect Vasc Surg Endovasc Ther. 2009 Dec;21(4):221-4; quiz 224-5. Epub 2010 Jan 3.

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:	May 2, 2012
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:

Postthrombotic Syndrome
Postphlebitic Syndrome
Thromboembolism
Thrombosis
Venous Thrombosis
Venous Thromboembolism
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
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on May 24, 2012