Clinical trial NCT00790335: Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis
Official title: Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis--The ATTRACT Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Deep Vein Thrombosis
Venous Thrombosis
Postphlebitic Syndrome
Venous Thromboembolism
Post Thrombotic Syndrome
Keywords: deep vein thrombosis
deep venous thrombosis
post thrombotic syndrome
blood clot
thrombolysis
tissue plasminogen activator
rt-PA
Activase
mechanical thrombectomy
pharmacomechanical
ATTRACT
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: McMaster University
name: Ontario Clinical Oncology Group (OCOG)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: BSN Medical Inc
name: Genentech, Inc.
name: Medtronic - MITG
name: Boston Scientific Corporation
name: Mid America Heart Institute
name: Society of Interventional Radiology Foundation
name: Massachusetts General Hospital
First posted: 2008-11-13
Enrollment: 692
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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).

Primary outcomes:
measure: Cumulative Incidence of Post-Thrombotic Syndrome (Villalta Scale)
timeFrame: Between 6 and 24 months after randomization
Secondary outcomes:
measure: Major Non-post-thrombotic Syndrome Treatment Failure
timeFrame: Through 24 months
measure: Any Treatment Failure
timeFrame: Through 24 months
measure: Moderate-to-severe Post-thrombotic Syndrome
timeFrame: Between 6 and 24 months after randomization
measure: Major Bleeding
timeFrame: Within 10 days after randomization
measure: Major Bleeding
timeFrame: Within 24 months after randomization
measure: Any (Minor + Major) Bleeding
timeFrame: Within 10 days after randomization
measure: Any (Major + Minor) Bleeding
timeFrame: Within 24 months after randomization
measure: Recurrent Venous Thromboembolism
timeFrame: Within 10 days after randomization
measure: Recurrent Venous Thromboembolism
timeFrame: Within 24 months after randomization
measure: Death
timeFrame: Within 10 days after randomization
measure: Death
timeFrame: Within 24 months after randomization
measure: Severity of Post-thrombotic Syndrome (Villalta)
timeFrame: At 6 months
measure: Severity of Post-thrombotic Syndrome (Villalta)
timeFrame: At 12 months
measure: Severity of Post-thrombotic Syndrome (Villalta)
timeFrame: At 18 months
measure: Severity of Post-thrombotic Syndrome (Villalta)
timeFrame: At 24 months
measure: Venous Clinical Severity Score
timeFrame: At 6 months
measure: Venous Clinical Severity Score
timeFrame: At 12 months
measure: Venous Clinical Severity Score
timeFrame: At 18 months
measure: Venous Clinical Severity Score
timeFrame: At 24 months
measure: Change in General Quality of Life - Physical
timeFrame: Baseline to 24 months post-randomization
measure: Change in General Quality of Life - Mental
timeFrame: Baseline to 24 months post-randomization
measure: Change in Venous Disease-specific Quality of Life
timeFrame: Baseline to 24 months post-randomization
measure: Change in Leg Pain Severity
timeFrame: Baseline to 10 days post-randomization
measure: Change in Leg Pain Severity
timeFrame: Baseline to 30 days post-randomization
measure: Change in Leg Circumference
timeFrame: Baseline to 10 days post-randomization
measure: Change in Leg Circumference
timeFrame: Baseline to 30 days post-randomization
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arrowhead Hospital/Phoenix Heart, PLLC
state: Arizona
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Danbury
country: United States
facility: Danbury Hospital
state: Connecticut
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Health Systems
state: Delaware
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Clearwater
country: United States
facility: Mease Countryside Hospital
state: Florida
city: Miami
country: United States
facility: Baptist Cardiac & Vascular Institute
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Tampa
country: United States
facility: Florida Hospital-Tampa Division-Pepin Heart Institute and Dr. Kiran C. Patel Research Institute
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Hinsdale
country: United States
facility: Adventist Midwest Health
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Winfield
country: United States
facility: Central DuPage Hospital
state: Illinois
city: Indianapolis
country: United States
facility: CorVasc
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Carver's College of Medicine
state: Iowa
city: Florence
country: United States
facility: St. Elizabeth Healthcare of Northern Kentucky
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Ann Arbor Veteran's Administration Health System
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: St. Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Saint Elizabeth Regional Medical Center
state: Nebraska
city: Teaneck
country: United States
facility: Holy Name Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New York
country: United States
facility: Cornell Weill Medical Center
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Toledo
country: United States
facility: Jobst Vascular Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital and Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Presbyterian Shadyside
state: Pennsylvania
city: Pittsburgh
country: United States
facility: The Western Pennsylvania Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: The Reading Hospital and Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Provo
country: United States
facility: Utah Valley Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Spokane
country: United States
facility: Sacred Heart Medical Center
state: Washington
city: La Crosse
country: United States
facility: Gundersen Clinic, Ltd.
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: Clinical Coordinating Center at Washington University School of Medicine
name: Suresh Vedantham, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Data Coordinating Center at McMaster University-Ontario Clinical Oncology Group
name: Clive Kearon, MB, MRCP, FRCP(C), PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Samuel Z Goldhaber, M.D.
role: STUDY_CHAIR
References:
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.
citation: Kahn SR. The post-thrombotic syndrome: the forgotten morbidity of deep venous thrombosis. J Thromb Thrombolysis. 2006 Feb;21(1):41-8. doi: 10.1007/s11239-006-5574-9.
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. doi: 10.1097/01.RVI.0000203802.35689.66. No abstract available.
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. doi: 10.1097/01.rvi.0000127894.00553.02.
citation: Li W, Kessinger CW, Orii M, Lee H, Wang L, Weinberg I, Jaff MR, Reed GL, Libby P, Tawakol A, Henke PK, Jaffer FA. Time-Restricted Salutary Effects of Blood Flow Restoration on Venous Thrombosis and Vein Wall Injury in Mouse and Human Subjects. Circulation. 2021 Mar 23;143(12):1224-1238. doi: 10.1161/CIRCULATIONAHA.120.049096. Epub 2021 Jan 15.
citation: Kahn SR, Julian JA, Kearon C, Gu CS, Cohen DJ, Magnuson EA, Comerota AJ, Goldhaber SZ, Jaff MR, Razavi MK, Kindzelski AL, Schneider JR, Kim P, Chaer R, Sista AK, McLafferty RB, Kaufman JA, Wible BC, Blinder M, Vedantham S; ATTRACT Trial Investigators. Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2020 Jan;8(1):8-23.e18. doi: 10.1016/j.jvsv.2019.03.023.
citation: Magnuson EA, Chinnakondepalli K, Vilain K, Kearon C, Julian JA, Kahn SR, Goldhaber SZ, Jaff MR, Kindzelski AL, Herman K, Brady PS, Sharma K, Black CM, Vedantham S, Cohen DJ. Cost-Effectiveness of Pharmacomechanical Catheter-Directed Thrombolysis Versus Standard Anticoagulation in Patients With Proximal Deep Vein Thrombosis: Results From the ATTRACT Trial. Circ Cardiovasc Qual Outcomes. 2019 Oct;12(10):e005659. doi: 10.1161/CIRCOUTCOMES.119.005659. Epub 2019 Oct 8.
citation: Weinberg I, Vedantham S, Salter A, Hadley G, Al-Hammadi N, Kearon C, Julian JA, Razavi MK, Gornik HL, Goldhaber SZ, Comerota AJ, Kindzelski AL, Schainfeld RM, Angle JF, Misra S, Schor JA, Hurst D, Jaff MR; ATTRACT Trial Investigators. Relationships between the use of pharmacomechanical catheter-directed thrombolysis, sonographic findings, and clinical outcomes in patients with acute proximal DVT: Results from the ATTRACT Multicenter Randomized Trial. Vasc Med. 2019 Oct;24(5):442-451. doi: 10.1177/1358863X19862043. Epub 2019 Jul 27.
citation: Kearon C, Gu CS, Julian JA, Goldhaber SZ, Comerota AJ, Gornik HL, Murphy TP, Lewis L, Kahn SR, Kindzelski AL, Slater D, Geary R, Winokur R, Natarajan K, Dietzek A, Leung DA, Kim S, Vedantham S. Pharmacomechanical Catheter-Directed Thrombolysis in Acute Femoral-Popliteal Deep Vein Thrombosis: Analysis from a Stratified Randomized Trial. Thromb Haemost. 2019 Apr;119(4):633-644. doi: 10.1055/s-0039-1677795. Epub 2019 Jan 30.
citation: Comerota AJ, Kearon C, Gu CS, Julian JA, Goldhaber SZ, Kahn SR, Jaff MR, Razavi MK, Kindzelski AL, Bashir R, Patel P, Sharafuddin M, Sichlau MJ, Saad WE, Assi Z, Hofmann LV, Kennedy M, Vedantham S; ATTRACT Trial Investigators. Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis. Circulation. 2019 Feb 26;139(9):1162-1173. doi: 10.1161/CIRCULATIONAHA.118.037425.
citation: Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, Magnuson E, Razavi MK, Comerota AJ, Gornik HL, Murphy TP, Lewis L, Duncan JR, Nieters P, Derfler MC, Filion M, Gu CS, Kee S, Schneider J, Saad N, Blinder M, Moll S, Sacks D, Lin J, Rundback J, Garcia M, Razdan R, VanderWoude E, Marques V, Kearon C; ATTRACT Trial Investigators. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med. 2017 Dec 7;377(23):2240-2252. doi: 10.1056/NEJMoa1615066.
citation: Vedantham S, Goldhaber SZ, Kahn SR, Julian J, Magnuson E, Jaff MR, Murphy TP, Cohen DJ, Comerota AJ, Gornik HL, Razavi MK, Lewis L, Kearon C. Rationale and design of the ATTRACT Study: a multicenter randomized trial to evaluate pharmacomechanical catheter-directed thrombolysis for the prevention of postthrombotic syndrome in patients with proximal deep vein thrombosis. Am Heart J. 2013 Apr;165(4):523-530.e3. doi: 10.1016/j.ahj.2013.01.024. Epub 2013 Mar 5.
citation: 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. doi: 10.1177/1531003509359311. Epub 2010 Jan 3.