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

Venous Thromboembolism Clinical Trial

— ATTRACT  

Official title:

Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis--The ATTRACT Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00790335
• Other study ID #: 22326953211
• Secondary ID: U01HL088476-01A1
• Status: Completed
• Phase: Phase 3
• First received: October 15, 2008
• Last updated: February 28, 2018
• Start date: November 2009
• Est. completion date: January 2017

Study information

• Verified date: February 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 692
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Deep Vein Thrombosis
• Post Thrombotic Syndrome
• Postphlebitic Syndrome
• Postthrombotic Syndrome
• Syndrome
• Thromboembolism
• Thrombosis
• Venous Thromboembolism
• Venous Thrombosis

Intervention

Drug:
• Recombinant tissue plasminogen activator (rt-PA)
Pharmacomechanical catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Ann Arbor Veteran's Administration Health System	Ann Arbor	Michigan
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	University of Maryland	Baltimore	Maryland
United States	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	Mease Countryside Hospital	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Danbury Hospital	Danbury	Connecticut
United States	Henry Ford Health System	Detroit	Michigan
United States	St. Elizabeth Healthcare of Northern Kentucky	Florence	Kentucky
United States	Arrowhead Hospital/Phoenix Heart, PLLC	Glendale	Arizona
United States	Adventist Midwest Health	Hinsdale	Illinois
United States	CorVasc	Indianapolis	Indiana
United States	University of Iowa Carver's College of Medicine	Iowa City	Iowa
United States	St. Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Gundersen Clinic, Ltd.	La Crosse	Wisconsin
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Baptist Cardiac & Vascular Institute	Miami	Florida
United States	Medical College of Wisconsin/Froedtert Hospital	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Cornell Weill Medical Center	New York	New York
United States	Christiana Care Health Systems	Newark	Delaware
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	St. Joseph Hospital	Orange	California
United States	Florida Hospital	Orlando	Florida
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	The Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center Presbyterian Shadyside	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health & Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Sacred Heart Medical Center	Spokane	Washington
United States	Southern Illinois University	Springfield	Illinois
United States	Stanford University Medical Center	Stanford	California
United States	Staten Island University Hospital	Staten Island	New York
United States	Florida Hospital-Tampa Division-Pepin Heart Institute and Dr. Kiran C. Patel Research Institute	Tampa	Florida
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Jobst Vascular Center	Toledo	Ohio
United States	Georgetown University Hospital	Washington	District of Columbia
United States	The Reading Hospital and Medical Center	West Reading	Pennsylvania
United States	Central DuPage Hospital	Winfield	Illinois
United States	Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (11)

Lead Sponsor	Collaborator
Washington University School of Medicine	Boston Scientific Corporation, BSN Medical Inc, Genentech, Inc., Massachusetts General Hospital, McMaster University, Medtronic - MITG, Mid America Heart Institute, National Heart, Lung, and Blood Institute (NHLBI), Ontario Clinical Oncology Group (OCOG), Society of Interventional Radiology Foundation

Country where clinical trial is conducted

United States, 

References & Publications (4)

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

Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. 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. doi: 10.1378/chest.08-0658. Erratum in: Chest. 2008 Oct;134(4):892. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative Incidence of Post-Thrombotic Syndrome (Villalta Scale)	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.	Between 6 and 24 months after randomization
Secondary	Major Non-post-thrombotic Syndrome Treatment Failure	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.	Through 24 months
Secondary	Any Treatment Failure	Composite of PTS and major non-PTS treatment failure	Through 24 months
Secondary	Moderate-to-severe Post-thrombotic Syndrome	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.	Between 6 and 24 months after randomization
Secondary	Major Bleeding	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).	Within 10 days after randomization
Secondary	Major Bleeding	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).	Within 24 months after randomization
Secondary	Any (Minor + Major) Bleeding	Clinically overt bleeding that occurred through 10 days post-randomization	Within 10 days after randomization
Secondary	Any (Major + Minor) Bleeding	Clinically overt bleeding that occurred within 24 months post-randomization	Within 24 months after randomization
Secondary	Recurrent Venous Thromboembolism	Proportion of patients with symptomatic recurrent venous thromboembolism (including DVT and/or PE)	Within 10 days after randomization
Secondary	Recurrent Venous Thromboembolism	Symptomatic recurrent venous thromboembolism (DVT and/or PE)	Within 24 months after randomization
Secondary	Death	All-cause mortality	Within 10 days after randomization
Secondary	Death	All-cause mortality	Within 24 months after randomization
Secondary	Severity of Post-thrombotic Syndrome (Villalta)	Mean Villalta scale score at the specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.	At 6 months
Secondary	Severity of Post-thrombotic Syndrome (Villalta)	Mean Villalta scale score at the specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.	At 12 months
Secondary	Severity of Post-thrombotic Syndrome (Villalta)	Mean Villalta scale score at specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.	At 18 months
Secondary	Severity of Post-thrombotic Syndrome (Villalta)	Mean Villalta scale score at specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.	At 24 months
Secondary	Venous Clinical Severity Score	Mean Venous Clinical Severity Score (VCSS) at the specified follow-up visit; range 0-27 (did not use compression item), higher score is worse	At 6 months
Secondary	Venous Clinical Severity Score	Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)	At 12 months
Secondary	Venous Clinical Severity Score	Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)	At 18 months
Secondary	Venous Clinical Severity Score	Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)	At 24 months
Secondary	Change in General Quality of Life - Physical	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.	Baseline to 24 months post-randomization
Secondary	Change in General Quality of Life - Mental	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.	Baseline to 24 months post-randomization
Secondary	Change in Venous Disease-specific Quality of Life	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.	Baseline to 24 months post-randomization
Secondary	Change in Leg Pain Severity	Likert pain scale ranging from 1-7, with higher scores representing a greater intensity of pain	Baseline to 10 days post-randomization
Secondary	Change in Leg Pain Severity	Likert pain scale ranging from 1-7, with higher scores representing a greater intensity of pain	Baseline to 30 days post-randomization
Secondary	Change in Leg Circumference	Mean calf circumference measured 10 cm below the tibial tuberosity	Baseline to 10 days post-randomization
Secondary	Change in Leg Circumference	Mean calf circumference measured 10 cm below the tibial tuberosity	Baseline to 30 days post-randomization

External Links

•   Below-Knee Elastic Compression Stockings to Prevent the Post Thrombotic Syndrome
•   Deep Vein Thrombosis
•   Predictors of the Post Thrombotic Syndrome During Long-Term Treatment of Proximal Deep Vein Thrombosis
•   The Long-Term Clinical Course of Acute Deep Vein Thrombosis