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

Completed

Phase 3 Results N/A

Trial Description

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

Conditions

Interventions

  • Tissue plasminogen activator (Activase┬«)Drug
    Other Names: Alteplase; tPA
    Intervention Desc: Thrombolytic
  • Recombinant tissue plasminogen activator (rt-PA) Drug
    Other Names: rt-PA; recombinant tissue plasminogen activator; Activase; Alteplase
    Intervention Desc: Pharmacomechanical catheter-directed thrombolysis, consisting of intrathrombus administration of rt-PA using a catheter/device.
    ARM 1: Kind: Experimental
    Label: A-Intervention
    Description: 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

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients will be randomized to one of two arms: 1) 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 and 2)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.

Outcomes

Type Measure Time Frame Safety Issue
Primary Cumulative incidence of Post-Thrombotic Syndrome (Villalta Scale)
Secondary 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; Major bleeding, symptomatic pulmonary embolism, recurrent venous thromboembolism, and death.
Secondary 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. within 24 months of randomization No
Secondary Major bleeding, symptomatic pulmonary embolism, recurrent venous thromboembolism, and death within 10 days and 24 months after randomization Yes

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