Post-Thrombotic Syndrome (PTS) develops frequently (25-50%) in patients with proximal deep vein thrombosis (DVT) despite the use of standard anticoagulant therapy. PTS leads to lifestyle-limiting symptoms, work disability, leg ulcers, quality of life (QOL) impairment, and major healthcare costs. Preliminary studies indicate that image-guided Endovascular Thrombus Removal procedures can rapidly restore deep venous patency and thereby prevent PTS in acute proximal DVT patients. However, these studies are limited by reliance upon surrogate anatomic outcome measures of limited clinical significance, non-randomized design, single-center design, and small sample size. For this reason, there currently exists major controversy within the medical community as to whether or not Endovascular Thrombus Removal should be routinely used in the first-line treatment of acute proximal DVT. The long-term goal of the proposed project is to determine whether Endovascular Thrombus Removal should be translated into widespread, first-line use in patients with acute DVT. In the proposed study, we will conduct a Phase III, multicenter, open label, assessor-blinded, randomized controlled trial entitled "Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT)" to determine whether the use of Pharmacomechanical Catheter-Directed Thrombolysis (PCDT), a state-of-the-art Endovascular Thrombus Removal method, results in a) a lower prevalence of PTS and b) superior quality of life (QOL), two clinically important treatment outcomes, in symptomatic, first episode, acute proximal DVT patients. The proposed research is both innovative and significant. The study will be the first multicenter randomized trial to evaluate a state-of-the-art image-guided endovascular strategy for the prevention of PTS. If the study establishes a favorable risk-benefit ratio for PCDT, this finding will fundamentally change clinical practice and enable prevention of PTS in thousands of DVT patients. If PCDT does not prevent PTS or if its risk-benefit ratio proves to be unfavorable, this finding will reduce or eliminate the routine use of a costly and potentially risky therapy. Hence, either outcome of the proposed study will greatly improve clinical practice and decrease morbidity in patients with acute DVT, a common blood disorder. Therefore, the study will clearly improve public health and advance the NHLBI's mission. Project Narrative: The ATTRACT Trial will determine whether Pharmacomechanical Catheter-Directed Thrombolysis can prevent the Post-Thrombotic Syndrome (PTS) in patients with Deep Vein Thrombosis (DVT). If the Trial is positive, this finding will conclusively validate the "Open Vein Hypothesis" and thereby a) immediately enable prevention of PTS, a common, morbid, and expensive condition, in thousands of DVT patients each year;and b) catalyze a fundamental shift towards a new treatment paradigm in which early venous thrombus removal is considered an essential element of initial DVT therapy. If the Trial is negative, this finding will eliminate the routine use of a costly and potentially dangerous therapy. Hence, either study outcome will decrease morbidity from DVT, improve public health, and advance the NHLBI's mission.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL088476-04
Application #
8077310
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Kindzelski, Andrei L
Project Start
2008-06-09
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$1,373,888
Indirect Cost
$536,848
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Vedantham, Suresh (2014) Treating infrainguinal deep venous thrombosis. Tech Vasc Interv Radiol 17:103-8
Kahn, Susan R; Comerota, Anthony J; Cushman, Mary et al. (2014) The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation 130:1636-61
Vedantham, Suresh; Goldhaber, Samuel Z; Kahn, Susan R et al. (2013) 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 165:523-530.e3
Vedantham, Suresh (2011) Preventing pediatric postthrombotic syndrome: preparing the way. J Vasc Interv Radiol 22:405-7
Comerota, Anthony J (2009) The ATTRACT trial: rationale for early intervention for iliofemoral DVT. Perspect Vasc Surg Endovasc Ther 21:221-4;quiz 224-5