Sequelae of DVT: Post-Thrombotic Syndrome
Published on: July 01, 2011
Dr. Vercellotti indicated no relevant conflicts of interest.
Study Title: Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT)
Sponsor: Washington University School of Medicine
Collaborators: McMaster University, Ontario Clinical Oncology Group, Bacchus Vascular, BSN Medical, Inc., Genentech, MEDRAD Interventional/Possis, Mid America Heart Institute, Society of Interventional Radiology Foundation VasCore at Massachusetts General Hospital
Clinicaltrial.gov Identifier: NCT00790335
Participating Centers: 57 institutions in the United States
Accrual Goal: 692 patients
Study Design: This is an open label, randomized study with efficacy and safety endpoints. Eligibility criteria include the following: patients who are 16 to 75 years old with a new (<14 day duration) symptomatic proximal deep-vein thrombosis (DVT) involving the iliac, common femoral, femoral vein, or a combination of these sites.
Arm A, Intervention: Pharmacomechanical catheter-directed thrombolysis (PCDT) with intrathrombus delivery of recombinant tissue plasminogen activator (rt-PA) into the DVT over a period of up to 24 hours using one of three rt-PA delivery methods. Before and after PCDT, patients will receive standard DVT therapy as in the control arm.
Arm B, Control: Initial anticoagulant therapy with unfractionated heparin, enoxaparin, dalteparin, or tinzaparin for at least five days, overlapped with long-term oral warfarin (target INR 2.0 - 3.0). Elastic compression stockings will be prescribed.
Primary Outcome Measures: Cumulative incidence of post-thrombotic syndrome assessed by the Villata scale within 24 months following randomization.
Secondary Outcome Measures: Efficacy: Severity of post-thrombotic syndrome (PTS), resolution of presenting DVT symptoms, the prevalence of valvular reflux and residual thrombus, the degree of clot lysis, and cost-effectiveness within 24 months of randomization. Safety: Major bleeding, symptomatic pulmonary embolism, recurrent venous thromboembolism, and death within 10 days and 24 months after randomization. This is designated as a safety issue.
Rationale: The purpose of this study is to determine if the use of adjunctive PCDT, which includes the intrathrombus administration of rt-PA, can prevent PTS in patients with symptomatic proximal DVT as compared with optimal standard DVT therapy alone. Rt-PA 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 capacity of rt-PA to lyse venous thrombus in patients with DVT and suggest that successful rt-PA-mediated thrombolysis can prevent PTS, a morbid, late complication of DVT that occurs in nearly 50 percent of patients.
Under imaging guidance, rt-PA is delivered directly into the venous thrombus using a catheter/device that is embedded within the thrombus. This method of rt-PA delivery, PCDT, is thought to be safer, more effective, and more efficient than other approaches. The question of whether PCDT using rt-PA improves long-term outcomes with acceptable risk and cost in patients with DVT has not been addressed. The ATTRACT trial will investigate the major clinical controversy of whether catheter-directed thrombolysis should be used routinely as part of first-line DVT therapy.
Comment: Despite optimum anticoagulation therapy, venous stasis syndrome, venous ulcers, and chronic leg swelling are common, costly sequelae of DVT. Why does PTS occur? Venous hypertension either primarily or secondarily underlies the pathophysiology, but inflammation, cytokines, and other factors likely play roles in the process. For several years the “open vein” hypothesis suggested that immediate thrombus removal may preserve venous valve function and prevent PTS. This study addresses many important questions regarding catheter-directed thrombolysis including safety, cost, and effectiveness in preventing PTS.
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