Acute Lower Extremity Native Artery or Bypass Graft Occlusion MedDRA version: 8.1 Level: LLT Classification code 10043628 Term: Thrombosis NOS
Conditions
Interventions
Product Name: Plasmin (Human)
Product Code: TAL-05-00018
Pharmaceutical Form: Powder for solution for infusion
CAS Number: 9001-90-5
Con
Sponsors
Talecris Biotherapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Stage 1:The primary objective is to evaluate the safety of Plasmin (Human) in escalating doses to patients with thrombosed infrainguinal native arteries or by-pass grafts. Selection of the 2 appropriate doses for Stage 2 will be based upon safety and arteriographic evidence of thrombolysis. Stage 2:The primary objective is to evaluate the safety and efficacy of 2 dosages of Plasmin in a blinded and randomized fashion in order to select the dose(s) for evaluation in Phase III trials. Arteriographic evidence of thrombolysis will be used as the efficacy variable for the selection of the appropriate dose(s) for Phase III. ; Secondary Objective: Secondary efficacy objectives are to 1) evaluate the avoidance of open surgical procedures at Day 30 ± 3 after Plasmin treatment; 2) assess physiologic reperfusion (Ankle-Brachial Index, [ABI] increase of = 0.15) at the end of Plasmin infusion, after intervention procedures, and at Days 1-2, 7 ± 1, 30 ± 3, and 3) assess graft patency by ultrasound at Day 7 ± 1 and Day 30 ± 3. ; Primary end point(s): The primary efficacy endpoint will be based on the arteriogram results from the central reading facility review. • Thrombolysis at the end of treatment (arteriogram #3) will be compared to baseline (arteriogram #1) evaluated using a scale of 90%. | — |
Countries
Bulgaria, Czech Republic, Germany, Hungary, United Kingdom
Outcome results
None listed