Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease

June 26, 2023 updated by: Inova Health Care Services
This investigation will be conducted in subjects >18 years of age with PAD. Platelet activation and aggregation, and biomarkers associated with platelet activation, oxidative stress, and inflammation will be assessed prior to initiation of study-HD statin therapy (baseline), after 8 weeks of high-dose statins and 24 hours and 8 weeks after high dose statin + evolocumab therapy

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Monoclonal antibodies against PCSK9 are innovative agents that provide very potent LDL reduction when administered on top of statins. PCSK9 antibodies prevent LDL receptor degradation and enhance circulatory LDL cholesterol clearance. High LDL is a major risk factor for PAD and therefore lipid-lowering therapy constitutes another important therapeutic intervention for patients with PAD. Evolocumab is a common PCSK-9 inhibitor that has been shown to reduce plasma LDL. In this study sixty subjects will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy to determine the effect of Repatha on markers of cholesterol, thrombosis, and inflammation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Sixty patients with symptomatic PAD, as evidenced by:

  • either intermittent claudication with ABI <0.90, or
  • peripheral arterial revascularization procedure, or
  • amputation due to atherosclerotic disease.

Description

Criteria: Inclusion Criteria:

Symptomatic PAD, as evidenced by either

  • intermittent claudication with ABI <0.90, or
  • peripheral arterial revascularization procedure, or
  • amputation due to atherosclerotic disease.
  • Subject may be of either sex and of any race, and must be >18 years of age.
  • Subject agrees to not participate in any other investigational or invasive clinical study for a period of 4 months during the study period
  • Subject must be willing and able to give appropriate informed consent.
  • The subject is able to read and has signed and dated the informed consent document including authorization permitting release of personal health information approved by the investigator's Institutional Review Board (IRB).

Exclusion Criteria:

  • Prior use of any PCSK9 inhibition treatment Participation in any investigational study within the last 60 days.
  • Severe renal dysfunction, defined as an eGFR <20 mL/min/1.73 m2 at screening
  • Active liver disease or hepatic dysfunction, defined as AST or ALT >3 x ULN as determined by central laboratory analysis at screening
  • Recipient of any major organ transplant (e.g., lung, liver, heart, bone marrow, renal)
  • Known major active infection or major hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction in the judgment of the investigator
  • Malignancy (except non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 10 years
  • Subject has received drugs via a systemic route that have known major interactions with background statin therapy within 1 month before randomization or is likely to require such treatment during the study period (e.g. cyclosporine, clarithromycin, HIV protease inhibitors, gemfibrozil)
  • Female subject who is unwilling to use at least 2 effective birth control methods for at least 1 month before screening and 15 weeks after the end of treatment with investigational products, unless the subject is sterilized or postmenopausal.
  • Subject is pregnant or breast feeding, or planning to become pregnant or to breastfeed during receipt of investigational products and within 15 weeks after the end of study treatment
  • Known previous hypersensitivity reaction/s to the investigational products' active components and excipients.
  • Subjects treated with any antithrombotic agents except aspirin.
  • Subject likely to not be available to complete all protocol-required study visits or procedures, to the best of the subject's and investigator's knowledge
  • History or evidence of any other clinically significant disorder, condition, or disease other than those outlined above that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Patients with peripheral artery disease receiving evolocumab + high dose statins

Adult patients with a history of Peripheral Artery Disease (PAD) defined as one or more of the following:

  • Documented history of PAD
  • Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma),
  • Carotid artery disease (defined as >50% stenosis or prior revascularization )
Drug: Evolocumab
Sixty subjects will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Difference Between ADP-induced % Maximum Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Time Frame: Change from week 8 (V2) to week 16 (V5)
Mean difference between 5uM ADP-induced % maximum platelet aggregation between V2 [after run-in period / 8 weeks of HD statin therapy] and V5 [end of study/ 8 weeks o]f continued HD statin therapy + evolocumab]
Change from week 8 (V2) to week 16 (V5)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Difference Between Collagen-induced Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Time Frame: Change from week 8 (v2) to week 16 (v5)
Mean difference between 4ug Collagen-induced platelet aggregation (%) between V2 [after run-in period / 8 weeks of HD statin therapy] and V5 [end of study/ 8 weeks of continued HD statin therapy + evolocumab]
Change from week 8 (v2) to week 16 (v5)
Difference Between SFFLRN-induced Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Time Frame: Change from week 8 (v2) to week 16 (v5)
Mean difference between SFFLRN-induced maximum platelet aggregation (%) between V2 [after run-in period / 8 weeks of HD statin therapy] and V5 [end of study/ 8 weeks of continued HD statin therapy + evolocumab]
Change from week 8 (v2) to week 16 (v5)
Difference Between Activated % P-selectin Positive Platelets Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Time Frame: Change from week 8 (v2) to week 16 (v5)
Mean difference in activated % P-selectin positive platelets between V2 [after run-in period / 8 weeks of HD statin therapy] and V5 [end of study/ 8 weeks o]f continued HD statin therapy + evolocumab]
Change from week 8 (v2) to week 16 (v5)
Difference in TEG MAKH Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Time Frame: Change from week 8 (v2) to week 16 (v5)
Mean difference TEG MAKH (platelet-fibrin clot strength) between V2 [after run-in period / 8 weeks of HD statin therapy] and V5 [end of study/ 8 weeks of continued HD statin therapy + evolocumab] Thromboelastography (TEG) is a viscoelastic hemostatic assay that measures the global viscoelastic properties of whole blood clot formation under low shear stress. TEG shows the interaction of platelets with the coagulation cascade (aggregation, clot strengthening, and fibrin cross-linking). MAKH is a measure of maximum platelet-fibrin clot strength. The normal range for MAKH is 53-68mm.
Change from week 8 (v2) to week 16 (v5)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Inova Health Care Services

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 11, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 29, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 9, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 14, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 16, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 26, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16-2584

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Peripheral Arterial Disease

Clinical Trials on Evolocumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings