A study to test the drug, Plasmin (Human), in patients with clots in large arteries of the lower leg

Phase 1

Conditions: acute peripheral arterial occlusion
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
MedDRA version: 16.1Level: LLTClassification code 10057525Term: Peripheral artery occlusionSystem Organ Class: 100000004866

Registration Number: EUCTR2010-019760-36-DE

Lead Sponsor: Grifols Therapeutics, Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 230

Inclusion Criteria

1. Unilateral limb ischemia: symptomatic, SVS acute ischemic Categories I and IIa
2. Onset of symptoms = 14 days
3. Thrombosed (non-embolic) infrainguinal graft (synthetic, autologous, or single outflow composite) or infrainguinal native artery. For native arteries, occlusions of = 10 cm in length are eligible.
4.Diagnosis of occlusive thrombus
a.Diagnosis of occlusive thrombus in the graft or artery by arteriography after informed consent is obtained
b.Baseline Arteriogram must show a popliteal artery that is open and filling with contrast within which to place the BOC balloon (only for groups I, J and M)
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 = 18 years
8. 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
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

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. Definitive flow on duplex ultrasound through the occluded segment at baseline
4. Cardiopulmonary resuscitation in the last year
5. Previous systemic or anaphylactoid allergy to contrast agent, streptokinase, or blood products (subjects allergic to shellfish or iodine are permitted to enter the study).
6. 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. The subject 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, l. Subtherapeutic levels of unfractionated heparin anticoagulation as indicated by partial thromboplastin time (aPTT) <50 seconds or activated clotting time (ACT) <300 seconds (subtherapeutic anticoagulation level may be corrected by administration of additional heparin). Testing (aPTT or ACT) may be repeated prior to randomization.
7. Active graft infection
8. Occlusion occurred within one month of synthetic graft placement.
9. Occlusion occurred within 6 months of autologous graft placement
10. A sequential composite graft with dual outflows to correct multiple occlusions
11. Deemed by the Investigator to be medically unable to tolerate open vascular procedure
12. Known prothrombotic state, e.g., anti-cardiolipin antibody, human immunodeficiency virus (HIV)-associated peripheral vascular disease
13. Known contraindication to heparin (e.g., history of heparin-induced thrombocytopenia)
14. 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.
15. 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.
16. Active cancer except non-malignant tumors or basal cell carcinoma
17. Previous treatment with Plasmin
18. 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
19. 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®)
20. Treatment with oral an

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluation of the safety and tolerability of different methods of administering Plasmin through analysis of major and minor bleeding events, deaths, AEs, SAEs, and abnormal laboratory values.;Primary end point(s): The proportion of subjects with >50% thrombolysis at the end of treatment compared to baseline by arteriography;Timepoint(s) of evaluation of this end point: 5 Hours and 15 hours;Secondary Objective: 1. Avoidance of major surgical revascularization, mechanical device thrombectomy, major amputation (ankle and above), and CDT with a PA in the affected extremity from end of treatment to Day 30.<br>2. Ankle brachial index (ABI) improvement of =0.15 at the end of treatment and/or at post intervention time point (if performed).<br>3. Assessment of blood flow in treated native artery or graft by ultrasound at the end of treatment or post-intervention and Day 30.<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 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(s) of evaluation of this end point: 30 days

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