Cardiovascular Disease, Hyperlipidemia
Conditions
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.
Interventions
DRUGEvolocumab
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.
DIAGNOSTIC_TEST18F-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.
DIAGNOSTIC_TESTCCTA
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.
DRUGOmnipaque
contrast agent for CCTA
DRUGMetoprolol
beta blocker to optimize heart rate during CCTA
DRUGNitroglycerin
premedication for CCTA
Sponsors
Amgen
Cedars-Sinai Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
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.
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.
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.
Omnipaque: contrast agent for CCTA
Metoprolol: beta blocker to optimize heart rate during CCTA
Nitroglycerin: premedication for CCTA | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Data corruption | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Evolocumab, F18-NaF PET, CCTA |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 22 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Continuous | 61.8 years STANDARD_DEVIATION 10.1 |
| BMI | 26.8 kg/m^2 STANDARD_DEVIATION 4.4 |
| Cholesterol level HDL cholesterol | 47.9 mg/dL STANDARD_DEVIATION 14.4 |
| Cholesterol level LDL cholesterol | 82.2 mg/dL STANDARD_DEVIATION 38.9 |
| Cholesterol level Total choleseterol | 155.8 mg/dL STANDARD_DEVIATION 46.1 |
| Cholesterol level Triglycerides | 137.6 mg/dL STANDARD_DEVIATION 81.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Medication ACEi or ARB | 15 Participants |
| Medication Aspirin | 29 Participants |
| Medication Beta blocker | 17 Participants |
| Medication Calcium channel blocker | 7 Participants |
| Medication Statin | 38 Participants |
| Plaque volume Calcified plaque volume | 109 mm^3 STANDARD_DEVIATION 134 |
| Plaque volume Low density non calcified plaque volume | 37 mm^3 STANDARD_DEVIATION 29 |
| Plaque volume Non calcified plaque volume | 607 mm^3 STANDARD_DEVIATION 347 |
| Plaque volume Total plaque volume | 716 mm^3 STANDARD_DEVIATION 431 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 47 participants |
| Risk factors Current smoker | 1 Participants |
| Risk factors Diabetes | 10 Participants |
| Risk factors Hypercholesterolemia | 42 Participants |
| Risk factors Hypertension | 25 Participants |
| Risk factors Prior CAD history | 4 Participants |
| Risk factors Prior CVA history | 1 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 55 |
| other Total, other adverse events | 3 / 55 |
| serious Total, serious adverse events | 0 / 55 |
Outcome results
Primary
Change in Noncalcified Coronary Artery Plaque Volume (NCPV)
Compare NCPV in mm\^3 measured on cardiac CT images as analyzed by quantitative software between the two assessments
Time frame: baseline (pre-treatment) and 18 months after of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Evolocumab, F18-NaF PET, CCTA | Change in Noncalcified Coronary Artery Plaque Volume (NCPV) | -45 mm^3 | Standard Deviation 64 |
Secondary
Change in Plaque Composition (Total, Calcified, Low Density Non Calcified)
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
Time frame: baseline (pre-treatment) and 18 months after of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab, F18-NaF PET, CCTA | Change in Plaque Composition (Total, Calcified, Low Density Non Calcified) | Changes in low density non calcified plaque volume | -17 mm^3 | Standard Deviation 24 |
| Evolocumab, F18-NaF PET, CCTA | Change in Plaque Composition (Total, Calcified, Low Density Non Calcified) | Changes in total plaque volume | -5 mm^3 | Standard Deviation 97 |
| Evolocumab, F18-NaF PET, CCTA | Change in Plaque Composition (Total, Calcified, Low Density Non Calcified) | Changes in calcified plaque volume | 40 mm^3 | Standard Deviation 56 |