A clinical trial to compare different administrations of the investigational drug Plasmin in patients with a clot in an artery of the lower leg.

Phase 2

Conditions: Health Condition 1: null- Patients With Acute Lower Extremity Native Artery orBypass Grafi Occlusion

Registration Number: CTRI/2011/04/001657

Lead Sponsor: Talecris Biotherapeutics Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 100

Inclusion Criteria

1. Unilateral limb ischemia: symptomatic, SVS acute ischemic Categories I and IIa

2. Onset of symptoms less than or equal to 14 days

3. Thrombosed (non-embolic) infrainguinal graft (synthetic, autologous, or single

outflow composite) or infrainguinal native artery. For native arteries, occlusions

of greater than or equal to 10 cm in length are eligible.

4. Diagnosis of occlusive thrombus in the graft or artery by arteriography after informed consent is obtained

5. Ability to access the thrombus with the infusion catheter and successfully embed

the infusion segment of the infusion catheter.

6. Subject must be able to give written informed consent prior to study entry

7. Age greater than or equal to 18 years

8. Women of child bearing potential must use adequate contraception for the duration

of the study and must have a negative pregnancy test prior to study entry

(Since there is no upper age limit defined for this trial for the CTRI registration purpose we have included the upper age limit to be considered as 99 years).

Exclusion Criteria

Exclusion Criteria
General
1. Any medical or social condition that may interfere with the subject successfully completing the study
2. Women who are pregnant or lactating, or first 10 days post-partum

Past Medical History
3. Cardiopulmonary resuscitation in the last year
4. Previous systemic or anaphylactoid allergy to contrast agent, streptokinase, or blood products (subjects allergic to shellfish or iodine are permitted to enter the study).

Contraindications To Thrombolysis
5. Ineligible for thrombolytic treatment for any reason. Specific exclusions include:
a. History of hemorrhagic stroke
b. Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack [TIA]) within the past year
c. Intracranial or spinal neuro-surgery or severe intracranial trauma in the past 3 months
d. Major surgery, organ biopsy, or major trauma within the past 10 days
e. Lumbar puncture or non-compressible arterial puncture in the past 10 days
f. Intra-ocular surgery within the past 10 days
g. Active gastrointestinal or organ bleeding. Minor bleeding such as normal menses, cystitis, or minor hemorrhoidal bleeding are not exclusions
h. Uncontrolled arterial hypertension, defined as a systolic blood pressure >180 millimeters of mercury (mmHg) or diastolic blood pressure >110 mmHg. Thesubject will be eligible if the hypertension is controlled at the time of study enrollment.
i. Known intracranial neoplasm, aneurysm, or arterio-venous malformation
j. Current bleeding diathesis
k. Platelet count <75 x 109/L Current Medical Status
6. Active graft infection
7. Occlusion occurred within one month of synthetic graft placement
8. Occlusion occurred within 6 months of autologous graft placement
9. A sequential composite graft with dual outflows to correct multiple occlusions
10. Deemed by the Investigator to be medically unable to tolerate open vascular procedure
11. Known prothrombotic state, e.g., anti-cardiolipin antibody, human immunodeficiency virus (HIV)-associated peripheral vascular disease
12. Known contraindication to heparin (e.g., history of heparin-induced thrombocytopenia)
13. Hemoglobin <10.0 g/dL (low hemoglobin at screening in the absence of active bleeding may be corrected by transfusion). Hemoglobin testing can be repeated.
14. Impaired renal function or renal disease that constitutes a contraindication to contrast arteriography, including a screen/baseline creatinine of >2.0 mg/dL. Creatinine may be repeated following hydration for prerenal azotemia.

Prior/Concurrent Therapy
15. Previous treatment with Plasmin
16. 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?), urokinase (UK, [Abbokinase®]) within the last 48 hours
17. Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within 5 days prior to study entry or at any time during the study, e.g., abciximab (ReoPro®),eptifibatide (Integrilin®) or tirofiban (Aggrastat®)
18. Treatment with oral anticoagulants (e.g., warfarin, acenocumarol), and with an international normalized ratio (INR) of >1.7 (elevated INR at screening may be corrected prior to study enrollment). INR testing can be repeated.
Others
19. Participation in another clinical study within 30 days prior to entry (imaging studies without investigative treatment are permitted), or concomita

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The proportion of subjects with 50% thrombolysis at the end of treatment compared to baseline by arteriography.Timepoint: 5 hr timepoint

Secondary Outcome Measures

Name	Time	Method
The incidence of major and minor bleeding events, deaths, adverse events, serious adverse events, and abnormal laboratory values as a measure of safety and tolerability.Timepoint: DAY 30