E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Peripheral Arterial Occlusion (acute PAO) is to peripheral vascular disease what acute coronary syndromes are to atherosclerotic heart disease and what stroke is to atherosclerotic cerebrovascular diease. "Leg attack", "heart attack", and "brain attack" alike, require prompt restoration of arterial blood flow in order to affect a minimization of symptoms, tissue damage, morbidity, and mortality. |
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MedDRA Classification |
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 |
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E.2.2 | Secondary objectives of the trial |
To evaluate: • Rate of arterial flow restoration at 4 hours after initiation of study drug • Rate of improvement in index limb ankle-brachial index (ABI) by ≥ 0.15 at 30 days • Change in Walking Impairment Questionnaire functional status scores from baseline at 30 days • Safety
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
a) The subject (or legally acceptable representative) must give written informed consent b) Age 18 years or older c) Arteriographically confirmed acute PAO of the lower extremity with onset of symptoms within 14 days prior to randomization d) Acute index limb ischemia classified as SVS/ISCVS Class I or IIA caused by occlusion of a native artery and/or bypass graft (vein or prosthetic). Only Class I subjects with abrupt onset of ischemic rest pain or abrupt onset/progression of lifestyle-limiting claudication are eligible. e) Acute PAO with a need for urgent surgical intervention to restore arterial blood flow in the event of unsuccessful thrombolytic therapy f) Available for follow-up assessments
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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 a hereditary bleeding disorder or known bleeding diathesis, major surgery or trauma, open chest massage, ocular 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 5 days prior to randomization h) Past participation in any alfimeprase clinical trial i) Pregnant, lactating, or actively menstruating women and women o child-bearing potential who are not using adequate contraceptive precautions (e.g. intrauterine device, oral contraceptives, barrier methods, or other contraception deemed adequate by the investigator) j) Investigator inability to advance guidewire through index occlusion k) Any other subject feature that in the opinion of the investigator should preclude study participation
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E.5 End points |
E.5.1 | Primary end point(s) |
PRIMARY ENPOINTS • 30 day open vascular surgery free rate
SECONDRY ENDPOINTS • Rate of arterial flow restoration at 4 hours after the initiation of first dose of study drug • Rate of improvement in ABI at 30 days • Change in WIQ functional status scores from the baseline at 30 days • Adverse events, serious adverse events, major bleeding events, ICH, Peripheral arterial embolic events, all cause mortality, surgical and endovascular procedures and amputation up to 30 days
EXPLORATORY ENDPOINTS • Length of hospital stay up to 30 days • Length of intensive care unit (ICU) stay up to 30 days • Rate of improvement in ABI at 90 and 180 days • Change in WIQ functional status scores from baseline at 90 and 180 days • Adverse events, all cause mortality, surgical and endovascular procedures, and amputation at 90 and 180 days
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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 | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
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 |