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

NCT04306081 | Unknown Phase 4 DMC FDA Drug

• 2 other identifiers: 20167764HS-16-00965
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

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).

Conditions

Peripheral Arterial Disease

Keywords

PAD; Hyperlipidemia; Claudication

Outcome Measures

Primary Outcomes (1)

• Evolocumab effect in pain free walking time (PFWT) in patients with PAD

  To evaluate change in pain free walking time (PFWT) in patients with PAD at baseline and after six months of therapy with Evolocumab. PFWT will be measured in minutes, using a graded treadmill Gardner protocol with a constant speed of 2 miles per hour, increasing by 2% grade every 2 minutes.

  six months

Secondary Outcomes (1)

• Evolocumab effect in maximal walking time (MWT) in patients with PAD

  six months

Other Outcomes (7)

• Evolocumab effect in lower extremity arterial perfusion in ankle-brachial indices (ABI).

  six months

• Evolocumab effect in lower extremity arterial perfusion pressure in post-exercise ankle-brachial indices.

  six months

• Evolocumab effect in lower extremity arterial perfusion pressure in Toe-Brachial pressure indices.

  six months

Study Arms (2)

Treatment Arm

EXPERIMENTAL

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.

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.

Control Arm

PLACEBO COMPARATOR

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.

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

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. 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

Also known as: Repatha

Treatment Arm

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

Also known as: Control

Control Arm

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Leonardo Clavijo: lead
• Amgen: collaborator

Study Sites (1)

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Hyperlipidemias; Intermittent Claudication

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Leonardo Clavijo, MD, PhD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jorge Caro, MPH

CONTACT

323-382-7646; Jorge.Caro@med.usc.edu

Melissa Ramos, RN

CONTACT

323-442-7983; Melissa.Ramos@med.usc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Study subjects will be randomized, to receive either evolocumab or placebo. Each participant will have equal chance of receiving evolocumab or placebo. The study participant, the care provider and the investigator will not know to which study arm the participant was assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associated Professor Cardiology, USC. Director Vascular Medicine and Peripheral Interventions Program Director, Interventional Cardiology Fellowship, University of Southern California

Model Details: This is a double-blinded, prospective, randomized, placebo-controlled study.

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: March 12, 2020
• Study Start: December 14, 2017
• Primary Completion: December 30, 2020
• Study Completion: March 30, 2021
• Last Updated: March 12, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)