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

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

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).