NCT04306081

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

Effect of Evolocumab in Functional Status and LDL Oxidation of Patients With Peripheral Arterial Disease (Evol-PAD)

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 86 (estimated)
• Sponsor: Leonardo Clavijo · Academic / Other
• Sex: All
• Age: 40 Years – 85 Years
• Healthy volunteers: Not accepted

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).

Detailed description

This is a double-blinded, prospective, randomized, study in eighty-six subjects with clinical ASCVD with PAD on background treatment with maximal tolerated dose of a statin. Subjects will be assessed based on their medical history and physical examination. Eligible subjects must meet all inclusion criteria and none of the exclusion criteria (listed below). There will be a treatment group and a placebo group, each with equal number of participants (n=43 patients in each group). After consent and enrollment, subjects will have a venous blood sample drawn to perform serum circulating biomarkers of oxidative stress as oxidized low density lipoprotein (oxLDL), oxidized glutathione : reduced glutathione (GSH:GSSG) and soluble CD36 (sCD36). We will then perform: functional walking measurements, pain free walking time (PFWT), and (maximal walking time (MWT), lower extremity arterial perfusion assessment (rest ABI/TBI, post-exercise ABI and bilateral TcPO2), and brachial endothelial function testing (after hyperemia). Subjects will receive monthly subcutaneous injections of Evolocumab 420 mg or placebo injection. The study participants will be seen at three months and six months for follow up and a final assessment at 26 +/-2 weeks, all tests will be repeated for comparison from baseline and/or placebo.

Conditions

• Peripheral Arterial Disease

Interventions

Type	Name	Description
DRUG	Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months.	The study subjects randomized to the treatment study arm will receive monthly subcutaneous injections of evolocumab 420 mg in the abdomen, thigh or upper arm. The study drug (evolocumab) prefilled injector pens are provided by Amgen
OTHER	Placebo 1milliliter (mL) Subcutaneous Injection pre-filled injector Pen x 3 monthly for 6 months.	The study subjects randomized to the treatment study arm will receive monthly subcutaneous injections of Placebo in the abdomen, thigh or upper arm. The Placebo prefilled injector pens are provided by Amgen

Timeline

• Start date: 2017-12-14
• Primary completion: 2020-12-30
• Completion: 2021-03-30
• First posted: 2020-03-12
• Last updated: 2020-03-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study