Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease

NCT03247972 | Terminated Results FDA Drug

• 1 other identifier: 16-2584
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Peripheral Arterial Disease

Outcome Measures

Primary Outcomes (1)

• 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)

  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 Outcomes (4)

• 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)

  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)

  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)

  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)

  Change from week 8 (v2) to week 16 (v5)

Study Arms (1)

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

Interventions

Evolocumab DRUG

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.

Patients with peripheral artery disease receiving evolocumab + high dose statins

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Inova Health Care Services: lead

Study Sites (1)

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Sinai Center for Thrombosis Research

kbliden@lifebridgehealth.org

443-244-1497

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: August 14, 2017
• Study Start: August 11, 2017
• Primary Completion: September 1, 2019
• Study Completion: October 1, 2019
• Last Updated: February 16, 2024
• Results First Posted: February 16, 2024

Record last verified: 2023-06

Locations

US (1)