Effect of Evolocumab on Coronary Atherosclerosis

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-19

Study Completion Date

2023-05-30

Brief Summary

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This study will quantify changes in coronary plaque volumes and plaque composition in patients treated with evolocumab.

Previous intravascular ultrasound studies have shown that treatment with a lipid-lowering PCSK9 enzyme inhibitor, such as evolocumab, to be associated with a reduction of the fatty deposits that cause plaque in the arteries, however, it is not known how evolocumab affects specific coronary plaque types and plaque inflammation.

Investigators will use quantitative assessment of non-invasive coronary computed tomography angiography (CCTA) and positron emission tomography (PET)imaging to evaluate functional changes in plaque burden, plaque composition and vascular inflammation before and after treatment with evolocumab.

Investigators propose to show that patients treated with evolocumab in combination with statins demonstrate a greater reduction of coronary non-calcified plaque volume, thereby reducing the number of future cardiac events.

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Detailed Description

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To evaluate the effect of evolocumab, patients who are taking Evolocumab plus another cholesterol-lowering medication (e.g statins), will undergo diagnostic testing including non-invasive coronary CT angiographic (CCTA) scans and positron emission tomography (PET) scans. The CCTA and PET scans will be done before and after being treated with evolocumab.

At the initial visit, standard imaging eligibility screening will take place, as well as blood sampling to test cholesterol levels and presence of proteins (biomarkers) associated with heart disease. A CCTA will be done (if not done for clinical purposes within the past 90 days) and a PET scan with administration of 18F-NaF injection will take place. Patients will receive the first injection of evolocumab and will be taught how to self-inject once or twice a month for 18 months.

After the initial visit, patients will self-inject evolocumab at approximately 6, 12 and 18 months in front of a medical professional for site monitoring and re-training. Labs will be drawn to assess blood components related to heart disease.

Follow-up phone calls will be made at approximately 1,3, 9, 15 months and approximately 3-7 days after their final on-site visit (18 months) to monitor safety and drug adherence.

The final visit (18 months after the initial visit) will involve another PET scan, CCTA and blood collection for biomarker testing.

Conditions

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Cardiovascular Disease Hyperlipidemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Early development, single-arm, prospective, open-label study of evolocumab injection in patients with calcified plaque in the coronary artery detected by CCTA. Fifty-five (55) evaluable subjects will be enrolled in the study.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Evolocumab, F18-NaF PET, CCTA

Evolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe).

Group Type EXPERIMENTAL

Evolocumab

Intervention Type DRUG

Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously.

Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector.

18F-NaF PET

Intervention Type DIAGNOSTIC_TEST

18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously.

CCTA

Intervention Type DIAGNOSTIC_TEST

CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe.

Omnipaque

Intervention Type DRUG

contrast agent for CCTA

Metoprolol

Intervention Type DRUG

beta blocker to optimize heart rate during CCTA

Nitroglycerin

Intervention Type DRUG

premedication for CCTA

Interventions

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Evolocumab

Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously.

Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector.

Intervention Type DRUG

18F-NaF PET

18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously.

Intervention Type DIAGNOSTIC_TEST

CCTA

CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe.

Intervention Type DIAGNOSTIC_TEST

Omnipaque

contrast agent for CCTA

Intervention Type DRUG

Metoprolol

beta blocker to optimize heart rate during CCTA

Intervention Type DRUG

Nitroglycerin

premedication for CCTA

Intervention Type DRUG

Other Intervention Names

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Repatha® PCSK9 inhibitor 18F sodium fluoride sodium fluoride PET Coronary computed tomography angiography contrast beta blocker vasodilator

Eligibility Criteria

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Inclusion Criteria

* Evidence by CCTA of noncalcified coronary artery plaque (\>440 mm3) and thoracic aorta atherosclerosis
* On-label indications for evolocumab treatment which includes the following criteria:

Those who have established cardiovascular disease defined as acute coronary syndrome, history of myocardial infarction, stable angina or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin.

Exclusion Criteria

* Creatinine \> 1.5 mg/dL prior to imaging
* History of allergy to iodine contrast agents
* Allergy to evolocumab or any other ingredients contained in study drug
* Pregnancy
* Women who are breastfeeding
* Active atrial fibrillation
* History of coronary artery bypass graft
* Inability to lie flat
* Inability or unwilling to give informed consent
* Major illness or life expectancy \<1 year
* Planned coronary revascularization or major non-cardiac surgery in the next 12 months
* Previously or currently on evolocumab

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No