EW-A-401 to Treat Intermittent Claudication

Inclusion Criteria

• •1. Adults greater than or equal to 21 years.
• •2. Limiting lower limb intermittent claudication due to infra-inguinal obstructive atherosclerosis, not optimal for catheter-based treatment.
• •3. Patient femoral artery inflow by radio contrast or magnetic resonance angiography within the previous 12 months.
• •4. Stable symptoms for at least 4 months.
• •5. Peak walking time (PWT) on standardized Gardner Exercise Treadmill Exam between 1 and 12 minutes.
• •6. Resting ankle-brachial systolic blood pressure index (ABI) less than 0.9 in the more-affected limb.
• •7. Bilateral PAD for subjects enrolled into Strata C-F with the less-affected limb having any of the following:
• •Resting or post-exercise ABI less than or equal to 0.9.
• •Typical intermittent claudication.
• •Infrainguinal obstructive atherosclerosis in a femoropopliteal and/or tibial artery greater than or equal to 70%.
• •Subjects enrolled into Strata A and B may have both unilateral or bilateral peripheral atherosclerotic disease.
• •* Breast: mammogram
• •* Cervix: Pap smear
• •* Colon: Colonoscopy
• •* Skin
• •* Lung: contrast chest CT scan
• •4. Proliferative retinopathy, severe non-proliferative retinopathy, advanced age-related macular degeneration, especially subjects with chorodial neovascularization, diabetic retinopathy, macular edema, or intraocular surgery within 3 months.
• •5. Limiting symptom on Gardner Exercise Treadmill Examination other than intermittent claudication.
• •6. Co-morbid conditions that limit exercise capacity:
• •* Severe arthritis affecting lower extremities
• •* Severe chronic obstructive pulmonary disease
• •* Angina pectoris greater than Canadian Angina Class 2
• •* Dyspnea greater than New York Heart Association Class II
• •7. Cardiovascular surgery or percutaneous revascularization within 4 months.
• •* Inclusion is permitted two or more months after successful iliac stenting in the presence of significant infra-inguinal atherosclerotic obstruction.
• •* Inclusion is permitted immediately after unsuccessful attempts at percutaneous recanalization of total occlusions of infra-inguinal arteries.
• •8. Coagulopathy:
• •* aPTT greater than 1.4 x mean laboratory normal reference range
• •* International Normalized Ration of Prothrombin Time greater than 1.5
• •* Patients on anticoagulation therapy are eligible to participate, with reversal of coagulopathy in accordance with ACC/AHA guidelines, except patients with: Recent arterial (0-1 month) thromboemboism; Recent venous (0-3 months) thromboembolism; Recurrent venous thromboembolism; Non-valvular atrial fibrillation and previous thromboembolism; Mechanical prosthetic valve.
• •9. Women of childbearing potential.
• •10. Subjects unwilling to use barrier contraception during the study.
• •11. Subjects unsuitable for unilateral investigational thigh compression for perfusion measurements due to:
• •* Patent femoropopliteal or femorotibial bypass graft or patent femoropopliteal stent on both limbs.
• •* Subjects with one of the above features who are amenable to contralateral thigh compression are eligible for enrollment.
• •12. Immune compromise including chronic HIV, HBV, and HCV infection.
• •13. Contraindication to Magnetic Resonance Imaging:
• •* Allergy to Gadolinium MRI contrast agents.
• •* Implanted cardiac pacemaker or defibrillator.
• •* Central nervous system aneurysm clips.
• •* Implanted neural stimulator.
• •* Cochlear implant.
• •* Ocular foreign body (e.g. metal shavings).
• •* Insulin Pump.
• •* Metal shrapnel or bullet.
• •* Note: When subjects can provide evidence that their implanted device is labeled compatible with MRI, exceptions to the above exclusions can be made and recorded in the note.
• •14. Creatinine clearance less than or equal to 20 mL per minute. Creatinine clearance (CLcr) will be estimated using the Cockcroft-Gault formula.
• •15. Current alcohol, drug abuse, severe medical, psychiatric, behavioral, or emotional disorder of any other condition that may preclude a subject from complying with all requirement of the protocol.
• •16. Subjects receiving experimental medication or participating in another study receiving an experimental drug or procedure within 30 days prior to enrollment.
• •17. Unable or unwilling to provide written informed consent.