A Study of Intra-thrombus Plasmin (Human) In Acute Peripheral Arterial Occlusion
Condition: Acute Peripheral Arterial Occlusion
MeSH terms: Arterial Occlusive Diseases
Intervention: Plasmin; Plasminogen Activator; Placebo
Intervention description: Plasmin prepared in 0.9% saline for injection; Plasminogen activator used according to the Investigator's clinical judgment.; Normal saline for injection at the same volume as the plasminogen activator.
Intervention MeSH terms: Plasminogen; Tissue Plasminogen Activator; Fibrinolysin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 174.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute Limb Ischemia

Summary:

      The primary purpose of this Phase 2 study is to optimize Plasmin delivery by comparing
      different delivery regimens in patients with peripheral arterial occlusion. The study
      includes a blinded plasminogen activator treatment group and a blinded plasminogen activator
      placebo group. The study will also assess safety and tolerability of Plasmin at 150 and 250
      mg doses.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Unilateral limb ischemia - Society of Vascular Surgery Categories I and IIa

          -  Onset of symptoms less than or equal to 14 days

          -  Thrombosed infrainguinal bypass graft or native artery

          -  Diagnosis by arteriography of occlusive thrombus in graft or artery

          -  Ability to embed the infusion catheter into the thrombus

          -  Women of childbearing potential must use contraception and have a negative pregnancy
             test

        Exclusion Criteria:

          -  Any medical or social condition that may interfere with study participation

          -  Women who are pregnant or lactating

          -  Hemorrhagic stroke history

          -  Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic
             attack) within one year

          -  Intracranial or spinal neurosurgery, or severe intracranial trauma in the last 3
             months

          -  Major surgery, organ biopsy, or major trauma within the past 10 days

          -  Lumbar puncture or non-compressible arterial puncture in the past 10 days

          -  Intraocular surgery within the past 10 days

          -  Active gastrointestinal or organ bleeding

          -  Uncontrolled arterial hypertension (systolic blood pressure >180 mmHg or diastolic
             blood pressure >110 mmHg)

          -  Known intracranial neoplasm, aneurysm, or arteriovenous malformation

          -  Current bleeding diathesis

          -  Platelet count <75 x 10e9/L

          -  Active graft infection

          -  Occlusion occurred within one month of synthetic graft placement

          -  Occlusion occurred within 6 months of autologous graft placement

          -  A sequential composite graft with dual outflows to correct multiple occlusions

          -  Medically unable to tolerate an open vascular procedure

          -  Known prothrombotic state

          -  Hemoglobin <10.0 g/dL

          -  Impaired renal function or renal disease that constitutes a contraindication to
             contrast angiography, including creatinine >2.0 mg/dL

          -  Treatment with a full dose plasminogen activator (PA) within the last 48 hours

          -  Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5
             days

          -  Treatment with oral anticoagulants, and with an international normalized ratio of >1.7