Arterial Occlusive Diseases
Conditions
Keywords
PAO, acute peripheral arterial occlusion, thrombolysis, blood clot, leg attack, alfimeprase, thrombus, embolism, thromboembolism, claudication, thrombolytic, thrombosis, plasminogen activator, arterial flow
Brief summary
The purpose of this study is to directly compare the safety and efficacy of intra-thrombus alfimeprase 0.3 mg/kg with placebo in acute peripheral arterial occlusion (PAO) as measured by a 30 day open vascular free surgery rate.
Detailed description
There is an unmet medical need to improve thrombolytic therapy in acute peripheral arterial occlusion (PAO). Currently used plasminogen activators can result in increased circulating levels of plasmin that result in a systemic lytic state that does not distinguish between physiologic and pathologic thrombosis. In general, mean plasminogen activator infusion durations of greater than 24 hours in order to achieve successful thrombolysis are problematic in a disease where delayed restoration of arterial flow can lead to irreversible ischemic damage. A direct thrombolytic agent like alfimeprase, with a rapid mechanism of action and a potentially safer bleeding risk profile, could facilitate a rapid restoration of arterial flow and avoidance of open vascular surgery.
Interventions
DRUGalfimeprase
Sponsors
ARCA Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or older * Arteriographically confirmed acute PAO of the lower extremity with onset of symptoms within 14 days prior to randomization * 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 * Acute PAO with a need for urgent surgical intervention to restore arterial blood flow in the event of unsuccessful thrombolytic therapy * Available for follow-up assessments
Exclusion criteria
* Contraindication to systemic anticoagulation * History of endovascular procedure or open vascular surgery on the index limb within the past 30 days * History of significant acute or chronic kidney disease that would preclude contrast angiography * Known allergy to contrast agents * History of heparin induced thrombocytopenia * Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to randomization * Any thrombolytic therapy within 5 days prior to randomization * Past participation in any alfimeprase trial * Pregnant, lactating, or actively menstruating women or women of childbearing potential who are not using adequate contraceptive precautions * Investigator inability to advance guidewire through index occlusion * Any other subject feature that in the opinion of the investigator should preclude study participation
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| rate of arterial flow restoration | — |
| rate of improvement in index limb ABI | — |
| change in WIQ functional status scores | — |
| AEs and SAEs | — |
| major bleeding events | — |
| ICH | — |
| peripheral arterial embolic events | — |
| all cause mortality | — |
| surgical and endovascular procedures | — |
| amputation | — |
| changes in chemistry, hematology, and coagulation parameters based on central laboratory measurements | — |
| anti-alfimeprase antibody | — |
Countries
United States
Outcome results
None listed