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

The Washington University

Status and phase: Completed; Phase 3

Conditions: Venous Thromboembolism; Postphlebitic Syndrome; Post Thrombotic Syndrome; Deep Vein Thrombosis; Venous Thrombosis

Treatments: Drug: Recombinant tissue plasminogen activator (rt-PA)

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00790335

22326953211

U01HL088476-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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

Enrollment: 692 patients

Sex: All

Ages: 16 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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692 participants in 2 patient groups

A-Intervention

Experimental group

Description:

PCDT with intrathrombus delivery of recombinant tissue plasminogen activator (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

Treatment:

Drug: Recombinant tissue plasminogen activator (rt-PA)

B-Control

No Intervention group

Description:

Initial anticoagulant therapy with unfractionated heparin, enoxaparin, dalteparin, or tinzaparin, for at least 5 days, overlapped with long-term oral warfarin (target international normalized ratio 2.0 - 3.0). Elastic compression stockings will be prescribed