Cardiovascular DiseasePhase 3NCT03689946
Effect of Evolocumab on Coronary Atherosclerosis
A Phase 3 study testing Evolocumab, 18F-NaF PET and CCTA in people with Cardiovascular Disease and Hyperlipidemia, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiovascular Disease, Hyperlipidemia
- What is being tested?
- Evolocumab, 18F-NaF PET and CCTA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Mar 2019to 30 May 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Cardiovascular Disease, Hyperlipidemia
- Being tested
- Evolocumab, 18F-NaF PET, CCTA, Omnipaque, Metoprolol
- Medical subject headings
- Cardiovascular Diseases, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
Also called Repatha®, PCSK9 inhibitor
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 PETDiagnostic test
Also called 18F sodium fluoride, sodium fluoride 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.
CCTADiagnostic test
Also called Coronary computed tomography angiography
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.
OmnipaqueDrug
Also called contrast
contrast agent for CCTA
MetoprololDrug
Also called beta blocker
beta blocker to optimize heart rate during CCTA
NitroglycerinDrug
Also called vasodilator
premedication for CCTA
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab, F18-NaF PET, CCTA | Experimental | 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). Receives: Drug: Evolocumab; Diagnostic Test: 18F-NaF PET; Diagnostic Test: CCTA; Drug: Omnipaque; Drug: Metoprolol; Drug: Nitroglycerin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline (pre-treatment) and 18 months after of treatment
Secondary outcomes (1)
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
Measured: baseline (pre-treatment) and 18 months after of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2018
- Study start19 Mar 2019
- Primary completion28 Jan 2023
- Study completion30 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Daniel S. Berman, Cedars-Sinai Medical Center
- Investigators
- Daniel S. Berman, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03689946
- Sponsor's protocol ID
- 54274
- Status last verified
- Jun 2024
- First submitted
- 27 Sep 2018
- Last updated
- 17 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Han D, Tzolos E, Park R, Gransar H, Hyun M, Friedman JD, Hayes SW, Thomson LEJ, Kwan AC, Budoff M, Shah PK, Kwiecinski J, Wetzel S, Findling C, Slomka PJ, Dey D, Tamarappoo BK, Berman DS. Effects of Evolocumab on Coronary Plaque Composition and Microcalcification Activity by Coronary PET and CT Angiography. JACC Cardiovasc Imaging. 2025 May;18(5):589-599. doi: 10.1016/j.jcmg.2025.01.005. Epub 2025 Apr 2.
PubMed 40178463
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03689946
- Acronym / sponsor ID
- 54274
- Conditions
- Cardiovascular Disease, Hyperlipidemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 19 Mar 2019 (actual)
- Primary completion
- 28 Jan 2023 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 1 Oct 2018 (actual)
- Results
- Posted 17 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Evolocumab, F18-NaF PET, CCTA | Experimental | Drug: Evolocumab, Diagnostic Test: 18F-NaF PET, Diagnostic Test: CCTA, Drug: Omnipaque, Drug: Metoprolol, Drug: NitroglycerinEvolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvolocumabAlso: Repatha®, PCSK9 inhibitorEvolocumab: 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. | Drug | Evolocumab, F18-NaF PET, CCTA |
| 18F-NaF PETAlso: 18F sodium fluoride, sodium fluoride PET18F-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 test | Evolocumab, F18-NaF PET, CCTA |
| CCTAAlso: Coronary computed tomography angiographyCCTA: 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. | Diagnostic test | Evolocumab, F18-NaF PET, CCTA |
| OmnipaqueAlso: contrastcontrast agent for CCTA | Drug | Evolocumab, F18-NaF PET, CCTA |
| MetoprololAlso: beta blockerbeta blocker to optimize heart rate during CCTA | Drug | Evolocumab, F18-NaF PET, CCTA |
| NitroglycerinAlso: vasodilatorpremedication for CCTA | Drug | Evolocumab, F18-NaF PET, CCTA |
Primary outcome
Change in Noncalcified Coronary Artery Plaque Volume (NCPV)
Time frame: 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
1 secondary outcome
Change in Plaque Composition (Total, Calcified, Low Density Non Calcified)
Time frame: baseline (pre-treatment) and 18 months after of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40178463Han D, Tzolos E, Park R, Gransar H, Hyun M, Friedman JD, Hayes SW, Thomson LEJ, Kwan AC, Budoff M, Shah PK, Kwiecinski J, Wetzel S, Findling C, Slomka PJ, Dey D, Tamarappoo BK, Berman DS. Effects of Evolocumab on Coronary Plaque Composition and Microcalcification Activity by Coronary PET and CT Angiography. JACC Cardiovasc Imaging. 2025 May;18(5):589-599. doi: 10.1016/j.jcmg.2025.01.005. Epub 2025 Apr 2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel S. Berman, MD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Evolocumab, 18F-NaF PET and CCTA in people with Cardiovascular Disease and Hyperlipidemia, run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Noncalcified Coronary Artery Plaque Volume (NCPV) (time frame: baseline (pre-treatment) and 18 months after of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03689946, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2024.