Effect of Evolocumab on Coronary Atherosclerosis

Phase 3

Completed

Conditions: Cardiovascular Disease
Hyperlipidemia

Interventions: Drug: Evolocumab
Diagnostic Test: 18F-NaF PET
Diagnostic Test: CCTA
Drug: Omnipaque
Drug: Metoprolol
Drug: Nitroglycerin

Registration Number: NCT03689946

Lead Sponsor: Cedars-Sinai Medical Center

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 55

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Evolocumab, F18-NaF PET, CCTA	18F-NaF PET	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).
Evolocumab, F18-NaF PET, CCTA	Omnipaque	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).
Evolocumab, F18-NaF PET, CCTA	Evolocumab	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).
Evolocumab, F18-NaF PET, CCTA	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).
Evolocumab, F18-NaF PET, CCTA	Nitroglycerin	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).
Evolocumab, F18-NaF PET, CCTA	Metoprolol	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).

Primary Outcome Measures

Name	Time	Method
Change in Noncalcified Coronary Artery Plaque Volume (NCPV)	baseline (pre-treatment) and 18 months after of treatment	Compare NCPV in mm\^3 measured on cardiac CT images as analyzed by quantitative software between the two assessments

Secondary Outcome Measures

Name	Time	Method
Change in Plaque Composition (Total, Calcified, Low Density Non Calcified)	baseline (pre-treatment) and 18 months after of treatment	Chances in volume of type of plaque (total, calcified, low density non calcified) on cardiac CT images as detected by quantitative software between the two assessments