E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute peripheral arterial occlusion (PAO) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10062599 |
|
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 the efficacy of alfimeprase compared with placebo as measured by 30 day open vascular surgery free rate |
|
E.2.2 | Secondary objectives of the trial |
To evaluate: -rate of arterial flow restoration at 4 hrs after initiation of study drug -rate of improvement in index limb-ankle-brachial index (ABI) by more than or equal to 0.15 at 30 days -change in the severity of planned surgical procedures at 30 days -change in index limb pain severity score at 30 days -30 day open vascular surgery free survival rate -length of hospital stay -length of intensive care unit stay -safety |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
-Subject (or legally acceptable representavtive) must give written informed consent -age 18 or older -acute PAO of the lower extremity with onset of symptoms within 14 days prior to randomization -acute limb ischemia classified as SVS/ISCVS Class I or IIA caused by occlusion of a native artery and/or bypass graft (vein or prosthetic) -need for open vascular surgical intervention in the event of unsuccessful thrombolysis -available for follow-up assessments |
|
E.4 | Principal exclusion criteria |
a) Contraindication to systemic anticoagulation e.g. history of documented hemorrhage requiring treatment within the past 30 days; history of hereditary bleeding disorder or known bleeding diathesis; major surgery or trauma, open chest massage, occular surgery or hemorrhagic retinopathy within the past 30 days; puncture at non-compressible site within 48 hours prior to administration of study drug; and history of stroke, intracranial hemorrhage, or central nervous system structural abnormalities within the past 3 months b) history of endovascular procedure or open vascular surgery on the index limb within the last 30 days c) History of significant acute or chronic kidney disease that would preclude contrast angiography d) known allergy to contrast agents e) history of heparin-induced thrombocytopenia (HIT) f) participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to randomization g) Any thrombolytic therapy within 30 days prior to randomization h) past participation in any alfimeprase clinical trial i) history of hypersensitivity to aspirin j) pregnant, lactating, or actively menstruating women and women of child-bearing potential who are not using adequte contraceptive precautions (e.g. intrauterine device, oral contraceptives, barrier methods or other contraception deemed adequate by the investigator) k) uncontrolled hypertension: systolic blood pressure (BP) more than 180 mmHg or diastolic BP more than 110mm Hg at the time of baseline assessment l) hematocrit less than 30%; subjects with a low hematocrit who are not actively bleeding can be entered into this study if after transfusion their hematocrit is greater than or equal to 30% m) platelet count less than 100 x 10(9)/L on baseline labs n) investigator inability to advance guidewire through index occlusion o) medically unable to withstand an open vascular surgical procedure p) any other subject feature that in the opinion of the investigator should preclude study participation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome measure is the 30 day open vascular surgery free rate. Only open vascular surgery performed on the index limb (i.e. limb affected by this episode of acute PAO) will be counted as an event of the endpoint. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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 | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Yes |
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 | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |