A Sequential Phase I/II Dose Escalation and Dose Selection Safety Study of Regional Intra-thrombus Plasmin (Human) Infusion In Acute Lower Extremity Native Artery or Bypass Graft Occlusion - PRIORITY

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 188

Inclusion Criteria

1. Age = 18 years.
2. 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.
3. Unilateral limb ischemia: symptomatic, SVS acute ischemic categories I and IIa.
4. Onset of symptoms less or equal to 14 days.
5. 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.
6. Diagnosis of occlusive thrombus in the graft or artery by arteriography after
Informed Consent is obtained.
7. Ability to traverse the thrombus with a guidewire.
8. Signed Informed Consent prior to study entry.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Clinical evidence of significant disease that may interfere with the patient
successfully completing the trial.
2. Women who are pregnant or lactating, or first 10 days post-partum.
3. Any medical or social condition which the investigator feels wil prohibit the subject from completing the trial
4. Cardiopulmonary resuscitation in the last 10 days.
5. Previous systemic or anaphylactoid allergy to contrast agent, streptokinase, or blood products.
6. Previous hemorrhagic stroke at any time.
7. Thrombotic or embolic stroke or cerebrovascular events (including transient
ischemic attack (TIA)) within one year.
8. Intracranial or spinal neuro-surgery or severe intracranial trauma in the last 3
months.
9. Major surgery, organ biopsy, or major trauma within the last 10 days.
10. Lumbar puncture or non-compressible arterial puncture in the last 10 days.
11. Intra-ocular surgery within the last 10 days.
12. Active gastrointestinal or organ bleeding. Minor bleeding such as normal menses,
cystitis, or minor hemorrhoidal bleeding are not exclusions.
13. Uncontrolled arterial hypertension, defined as a systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg.
14. Known intracranial neoplasm, aneurysm, or arterio-venous malformation.
15. Current bleeding diathesis.
16. Platelet count < 75 x 10 exp 9 P/L.
17. Graft infection.
18. Occlusion of a new synthetic or autologous graft within 6 months of placement. A
sequential composite graft with dual outflows to correct multiple occlusions is also ineligible.
19. Medically unable to tolerate open vascular procedure.
20. Known prothombotic state, e.g. anti-cardiolipin antibody, HIV-associated peripheral vascular disease.
21. Known contraindication to heparin (e.g. history of heparin-induced thrombocytopenia.)
22. Hemoglobin < 10.0 g/dL (low hemoglobin at screening in the absence of active
bleeding may corrected by transfusion).
23. Impaired renal function or renal disease that constitutes a contraindication to contrast angiography., including a screen/baseline creatinine of >2.0 mg/dL or subjects on renal dialysis

24. Previous treatment with Plasmin.
25. Treatment with full dose plasminogen activator (e.g., streptokinase (e.g., Streptase®, Kabikinase®), anistreplase (Eminase®), alteplase (e.g., Activase®), reteplase (e.g., Retavase®), tenecteplase (TNKase™), UK (Abbokinase®)) within the last 48 hours.
26.Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5 days, for example, abciximab (ReoPro®), eptifibatide (Integrilin®) or tirofiban (Aggrastat®).
27.Treatment with warfarin (Coumadin®) and with an INR of >1.7 (elevated INR at screening may be corrected prior to study enrollment.)
28. Participation in another clinical trial within 30 days prior to entry (imaging studies
without investigative treatment are permitted), or concomitant participation in
another trial or study.
29. Mentally challenged adult subjects who cannot give independent informed consent.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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