NCT02959047

Brief Summary

Peripheral arterial disease (PAD) is characterized by lower limb arterial obstruction due to atherosclerosis. Magnetic resonance imaging (MRI) methods can accurately quantify atherosclerotic plaque in the superficial femoral artery (SFA) in patients with PAD. Such techniques have demonstrated plaque regression with statin therapy over 1 year. Alirocumab is a PCSK9 inhibitor that effectively reduces LDL cholesterol up to 70% in patients on statins or intolerant to statins. The investigators hypothesize that effective low density lipoprotein (LDL) lowering with Alirocumab 150m subcutaneously (SQ) every 2 weeks will regress atherosclerotic plaque in the SFA in patients with PAD over one year compared to placebo. 54 patients with mild-moderate PAD (ankle brachial index or ABI 0.4-0.9) will be randomized to alirocumab 150 mg SQ every 2 weeks or matching placebo at the University of Virginia (UVA) (n=34) and Northwestern (n=20). The primary endpoint is change in atherosclerotic plaque volume in the superficial femoral artery over the 1 year treatment period. Secondary endpoints include changes in peak calf muscle perfusion after thigh cuff occlusion/hyperemia, 6-minute walk distance, and blood biomarkers (LDL cholesterol, fibrinogen, high sensitivity c-reactive protein (hs-CRP), and lipoprotein(a).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jul 2017

Longer than P75 for phase_4

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 4, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 8, 2016

Completed
8 months until next milestone

Study Start

First participant enrolled

July 17, 2017

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 8, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 8, 2023

Completed
Last Updated

May 10, 2023

Status Verified

May 1, 2023

Enrollment Period

5.8 years

First QC Date

November 4, 2016

Last Update Submit

May 8, 2023

Conditions

Peripheral Arterial Disease

Keywords

MRIPCSK9 inhibitionLDL cholesterol

Outcome Measures

Primary Outcomes (1)

  • Change in superficial femoral plaque volume (summed from both legs)

    Measured by black blood MRI, expressed in cm3

    1 year

Secondary Outcomes (7)

  • Change in calf muscle perfusion in the most symptomatic leg

    1 year

  • Change in plaque characteristics

    1 year

  • Change in 6-minute walk test

    1 year

  • Change in LDL cholesterol

    1 year

  • Change in high sensitivity c-reactive protein

    1 year

  • +2 more secondary outcomes

Study Arms (2)

Alirocumab

EXPERIMENTAL

Alirocumab 150mg SQ every 2 weeks

Drug: Alirocumab

Placebo

PLACEBO COMPARATOR

Matched placebo

Drug: Matching placebo

Interventions

AlirocumabDRUG

150mg SQ every 2 weeks

Also known as: Praluent
Alirocumab
Matching placeboDRUG

SQ every 2 weeks

Placebo

Eligibility Criteria

Age35 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 35-85
  • Clinical diagnosis of peripheral arterial disease
  • Ankle brachial index of 0.4-0.9
  • Either on statin for at least 6 months or statin intolerant. The statin used should be a high potency statin (Crestor, Lipitor) or high dose of a lower potency statin (e.g. Zocor 40-80mg, Pravachol 40-80 mg)

You may not qualify if:

  • rest pain
  • critical limb ischemia
  • known or planned stent in the SFA
  • known occlusion of the SFA
  • planned revascularization within the next year
  • inability to lie flat
  • known contraindications to MRI including pacemaker, implantable cardioverter defibrillators, certain intracranial aneurysm clips, claustrophobia
  • pregnancy
  • known allergy to alirocumab

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

  • Rrapo-Kaso E, Loffler AI, Petroni GR, Meyer CH, Walker M, Kay JR, DiMaria JM, Domanchuk K, Carr JC, McDermott MM, Kramer CM. Alirocumab and plaque volume, calf muscle blood flow, and walking performance in peripheral artery disease: A randomized clinical trial. Vasc Med. 2023 Aug;28(4):282-289. doi: 10.1177/1358863X231169324. Epub 2023 Apr 24.

    PMID: 37093712RESULT

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

alirocumab

Condition Hierarchy (Ancestors)

AtherosclerosisArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular DiseasesPeripheral Vascular Diseases

Study Officials

  • Christopher M Kramer, MD

    University of Virginia Health System

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Department of Medicine, Cardiology

Study Record Dates

First Submitted

November 4, 2016

First Posted

November 8, 2016

Study Start

July 17, 2017

Primary Completion

May 8, 2023

Study Completion

May 8, 2023

Last Updated

May 10, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will not share

Locations

US(2)