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

NCT ID: NCT04306081

Last Updated: 2020-03-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-14
• Study Completion Date: 2021-03-30

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Treatment Arm

43 Patients with lower extremities Peripheral Arterial Disease on maximum statin therapy will receive in addition a monthly dose of evolocumab 420 mg via subcutaneous injections for 6 months.

Group Type: EXPERIMENTAL

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.

Intervention Type: DRUG

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

Control Arm

43 Patients with lower extremities Peripheral Arterial Disease on maximum statin therapy will receive in addition a monthly dose of placebo via subcutaneous injections for 6 months.

Group Type: PLACEBO_COMPARATOR

Placebo 1milliliter (mL) Subcutaneous Injection pre-filled injector Pen x 3 monthly for 6 months.

Intervention Type: OTHER

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

Interventions

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

Intervention Type: DRUG

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

Intervention Type: OTHER

Other Intervention Names

Repatha; Control

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Leonardo Clavijo

OTHER

Sponsor Role: lead

Responsible Party

Leonardo Clavijo

Associated Professor Cardiology, USC. Director Vascular Medicine and Peripheral Interventions Program Director, Interventional Cardiology Fellowship, University of Southern California

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Leonardo Clavijo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

University of Southern California

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jorge Caro, MPH

Role: CONTACT

Jorge.Caro@med.usc.edu

323-382-7646

Melissa Ramos, RN

Role: CONTACT

Melissa.Ramos@med.usc.edu

323-442-7983

Facility Contacts

Jorge Caro, MPH

Role: primary

Jorge.Caro@med.usc.edu

323-382-7646

Melissa Ramos, RN

Role: backup

Melissa.Ramos@med.usc.edu

323-442-7983

Other Identifiers

HS-16-00965

Identifier Type: OTHER

Identifier Source: secondary_id

20167764

Identifier Type: -

Identifier Source: org_study_id