E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute peripheral arterial occlusion |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057525 |
E.1.2 | Term | Peripheral artery occlusion |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate safety, tolerability and ability to achieve thrombolysis of six different methods of administering Plasmin(Human) in patients with acute peripheral arterial occlusion. |
Efficacy Objective: Evaluation of six methods of administering 150 mg of Plasmin and plasminogen activator (PA) and PA Placebo in achieving thrombolysis and other exploratory efficacy measures in subjects with thrombosed infrainguinal native arteries or grafts |
|
E.2.2 | Secondary objectives of the trial |
- 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
- 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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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 |
|
E.4 | Principal 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. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |