Clinical trial NCT03689946: Effect of Evolocumab on Coronary Atherosclerosis
Official title: Effect of Evolocumab on Coronary Artery Plaque Volume and Composition by Coronary CTA (CCTA) and Microcalcification by F18-NaF PET: A Phase 3 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Disease
Hyperlipidemia
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2018-10-01
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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 purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Noncalcified Coronary Artery Plaque Volume (NCPV)
timeFrame: baseline (pre-treatment) and 18 months after of treatment
Secondary outcomes:
measure: Change in Plaque Composition (Total, Calcified, Low Density Non Calcified)
timeFrame: baseline (pre-treatment) and 18 months after of treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Daniel S. Berman, MD
role: PRINCIPAL_INVESTIGATOR
References: