Effect of Evolocumab in Functional Status and LDL Oxidation of Patients With Peripheral Arterial Disease

• Status: Recruiting
• Trial end date: 2021-03-30
• Target enrollment: 0
• Participant gender: All

Summary

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerotic cardiovascular disease (ASCVD) and is associated with increase cardiovascular risk. PAD impairs quality of life due to symptoms of claudication, pain at rest or risk of limb loss.

All major societies recognize the importance of LDL reduction in patients with PAD.

Statin therapy improves cardiovascular end-points in patients with PAD and have been shown to improve symptoms of lower extremity intermittent claudication (pain free walking time), 6-minute walking time, ankle-brachial index (ABI), and endothelial function, while decreasing markers of atherosclerosis.

This study aims to demonstrate that in patients with PAD on stable maximal tolerated lipid lowering regimen with a statin, further reduction of LDL with the pro protein converts subtilisin/kexin type 9 (PCSK-9) inhibitor Evolocumab, improves functional status (pain free walking time in particular, but also maximal walking time), lower extremity arterial perfusion and endothelial function (brachial endothelial reactivity).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Leonardo Clavijo
• Collaborator: Amgen
• Treatments: Antibodies, Monoclonal; Evolocumab

Criteria

Inclusion Criteria:

• Signed informed consent.

• Age ≥40 to ≤85 years of age at the time of consent.

• Diagnosis of ASCVD with peripheral arterial disease, Rutherford class I-VI at the time of diagnosis, confirmed by ABI≤0.9 at rest or ABI≤0.8 after exercise, angiography, duplex ultrasound or history of lower extremity surgical or endovascular revascularization.

• At least 1 months from last intervention, including surgery or endovascular procedures.

• Stable on maximal tolerated doses of a lipid-lowering regimen for at least 4 weeks.

• Most recent fasting LDL-C ≥55 mg/dL or non-HDL-C ≥80 mg/dL.

Exclusion Criteria:

• Subjects with active, non-healed wounds.

• Subjects with anticipated need of cardiac or surgical revascularization procedures.

• Subjects with chronic inflammatory conditions or requiring chronic systemic corticosteroids.

• New York Heart Association (NYHA) class III or IV heart failure, or known left ventricular ejection fraction <30%.

• Uncontrolled arrhythmia.

• Uncontrolled hypertension with systolic BP>180 mmHg or diastolic >100 mmHg.

• Untreated thyroid disease.

• Severe chronic renal disease with estimated glomerular filtration rate (eGFR) <20 mL/min.

• Liver disease with aspartame aminotransferase (AST) or alanine aminotransferase (ALT) ≥3 times the upper limit of normal.

• Status post-organ transplant.

• Pregnant and breastfeeding women

• Fertile age female not on appropriate birth control.

• Clinically significant disease that, in the opinion of the Principal Investigator, is likely to require surgery or immunotherapy that may interfere with the completion of the study.

• Active cancer or life expectancy of less than two years.

• Chronic anticoagulation or hypercoagulability disorder.

• Atrial fibrillation with a CHADS-VASc Score ≥2 or any clinical condition which, in the opinion of the Principal Investigator increases the risk of cerebrovascular events.