A Dose Escalation and Safety Study of Plasmin (Human) In Acute Lower Extremity Native Artery or Bypass Graft Occlusion (PRIORITY)

Inclusion Criteria:

• Age ≥ 18 years.
• Women of childbearing potential must use adequate contraception for the duration of the study and must have a negative pregnancy test prior to study entry.
• Unilateral limb ischemia: SVS acute ischemia Category I or IIa.
• Onset of symptoms </= 14 days.
• Thrombosed (non-embolic) infrainguinal graft (synthetic, autologous, or single outflow composite) or infrainguinal native artery. For native arteries, only occlusions of ≥ 10 cm in length are eligible.
• Diagnosis of occlusive thrombus in the graft or artery by arteriography after Informed Consent is obtained.
• Ability to traverse the thrombus with a guidewire.
• Signed informed consent prior to study entry.

Exclusion Criteria:

• Clinical evidence of significant disease that may interfere with the patient successfully completing the trial.
• Women who are pregnant or lactating, or first 10 days post-partum.
• Previous hemorrhagic stroke at any time. Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack (TIA)) within one year.
• Intracranial or spinal neuro-surgery, or severe intracranial trauma in the last 3 months. Major surgery, organ biopsy, or major trauma within the last 10 days. Lumbar puncture or non-compressible arterial puncture in the last 10 days. Intra-ocular surgery within the last 10 days.
• Current bleeding diathesis. Active gastrointestinal or organ bleeding. Minor bleeding such as normal menses, cystitis, or minor hemorrhoidal bleeding are not exclusions.
• Uncontrolled arterial hypertension, defined as a systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg.
• Known intracranial neoplasm, aneurysm, or arterio-venous malformation.
• Platelet count < 75 x 10e9/L.
• Occlusion of a graft within 6 months of placement.
• Medically unable to tolerate an open vascular procedure.
• Known prothrombotic condition.
• Hemoglobin <10.0 g/dL
• Impaired renal function or renal disease that constitutes a contraindication to contrast angiography, including creatinine > 2.0 mg/dL or subjects on renal dialysis.
• Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5 days, for example, abciximab (ReoPro®), eptifibatide (Integrilin®) or tirofiban (Aggrastat®).
• Treatment with warfarin (Coumadin®) and with an INR of >1.7 (elevated INR at screening may be corrected prior to study enrollment.)