A Phase 2, Randomized, Open-label (with Blinded Plasminogen Activator and Placebo Control Groups) Study to Evaluate the Effects of Different Intra-thrombus Infusion Regimens of Plasmin (Human) Compared to Plasminogen Activator and Placebo In Patients With Acute Lower Extremity Native Artery or Bypass Graft Occlusio
- Conditions
- acute peripheral arterial occlusionMedDRA version: 14.1Level: LLTClassification code 10057525Term: Peripheral artery occlusionSystem Organ Class: 10047065 - Vascular disorders
- Registration Number
- EUCTR2010-019760-36-HU
- Lead Sponsor
- Grifols Therapeutics, Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
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 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 = 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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).
5. Ineligible for thrombolytic treatment for any reason
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.
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate safety, tolerability and ability to achieve thrombolysis of six different methods of administering Plasmin(Human) in patients with acute peripheral arterial occlusion.;Secondary Objective: - To detemine the proportion of patients who avoid major surgical revascularization, mechanical device thrombectomy, and CDT with a PA in the affected extremity from end of treatment to Day 30 and<br>- To measure Ankle brachial index (ABI) improvement of = 0.15 at the end of treatment and/or at post intervention time point (if performed) and to assess blood flow in treated native artery or graft by ultrasound at the end of treatment or post-intervention and Day 30.;Primary end point(s):
- Secondary Outcome Measures
Name Time Method