Atherosclerotic Vascular Disease
Conditions
Brief summary
The purpose of this study is to evaluate the utility of 18Fluorine Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) as a tool to quantify atherosclerotic plaque.
Interventions
DRUGatorvastatin
Participants will be asked to self-administer one atorvastatin 10 mg or 80 mg tablet at approximately the same time each day.
DRUGplacebo
Participants will be asked to self-administer one tablet of placebo to atorvastatin 10 mg or 80 mg at approximately the same time each day.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female ages 30 to 80 * Participant is on a low dose statin for at least 6 weeks prior to screening or is statin-naive at screening
Exclusion criteria
* Participant has human immunodeficiency virus (HIV), Hepatitis B or C * Participant uses illegal drugs * Participant has Type I diabetes * Participant has a history of claustrophobia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction From Baseline in TBRmeanmax of the Qualifying Segment | Baseline and Week 12 | Vascular plaque inflammation was measured by 18FDG-PET imaging. Uptake of FDG by the carotid and thoracic aorta is expressed as the target, vessel wall to background, lumen ratio (TBR). TBRmax of an axial cross section of a vessel (a slice) is defined as the maximum TBR within a slice and TBRmeanmax is the mean of TBRmax for all slices in the qualifying segment. The qualifying segment is the left or right carotid or thoracic aorta with the greatest FDG uptake value at Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction From Baseline in TBRmeanmax of the Qualifying Segment in Statin-naive Participants | Baseline and Week 12 | Vascular plaque inflammation was measured by 18FDG-PET imaging. Uptake of FDG by the carotid and thoracic aorta is expressed as the target, vessel wall to background, lumen ratio (TBR). TBRmax of an axial cross section of a vessel (a slice) is defined as the maximum TBR within a slice and TBRmeanmax is the mean of TBRmax for all slices in the qualifying segment. The qualifying segment is the left or right carotid or thoracic aorta with the greatest FDG uptake value at Baseline. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 10 mg Atorvastatin Participants self-administered one 10 mg atorvastatin tablet and one 80 mg atorvastatin matching placebo tablet orally once daily for 12 weeks. | 42 |
| 80 mg Atorvastatin Participants self-administered one 80 mg atorvastatin tablet and one 10 mg atorvastatin matching placebo tablet orally once daily for 12 weeks. | 41 |
| Total | 83 |
Baseline characteristics
| Characteristic | 10 mg Atorvastatin | 80 mg Atorvastatin | Total |
|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 9.63 | 59.1 years STANDARD_DEVIATION 9.24 | 59.5 years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Male | 33 Participants | 32 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 42 | 8 / 41 |
| serious Total, serious adverse events | 1 / 42 | 1 / 41 |
Outcome results
Primary
Percent Reduction From Baseline in TBRmeanmax of the Qualifying Segment
Vascular plaque inflammation was measured by 18FDG-PET imaging. Uptake of FDG by the carotid and thoracic aorta is expressed as the target, vessel wall to background, lumen ratio (TBR). TBRmax of an axial cross section of a vessel (a slice) is defined as the maximum TBR within a slice and TBRmeanmax is the mean of TBRmax for all slices in the qualifying segment. The qualifying segment is the left or right carotid or thoracic aorta with the greatest FDG uptake value at Baseline.
Time frame: Baseline and Week 12
Population: The analysis population includes all participants who completed the study and had complete image sets with usable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 10 mg Atorvastatin | Percent Reduction From Baseline in TBRmeanmax of the Qualifying Segment | 1.4 Percent reduction |
| 80 mg Atorvastatin | Percent Reduction From Baseline in TBRmeanmax of the Qualifying Segment | 5.8 Percent reduction |
Comparison: Constrained longitudinal data analysis (cLDA)p-value: 0.006cLDA
p-value: 0.277cLDA
p-value: 0.08890% CI: [-1, 9.6]cLDA
Secondary
Percent Reduction From Baseline in TBRmeanmax of the Qualifying Segment in Statin-naive Participants
Vascular plaque inflammation was measured by 18FDG-PET imaging. Uptake of FDG by the carotid and thoracic aorta is expressed as the target, vessel wall to background, lumen ratio (TBR). TBRmax of an axial cross section of a vessel (a slice) is defined as the maximum TBR within a slice and TBRmeanmax is the mean of TBRmax for all slices in the qualifying segment. The qualifying segment is the left or right carotid or thoracic aorta with the greatest FDG uptake value at Baseline.
Time frame: Baseline and Week 12
Population: The analysis population includes all statin-naive participants who completed the study and had complete image sets.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 10 mg Atorvastatin | Percent Reduction From Baseline in TBRmeanmax of the Qualifying Segment in Statin-naive Participants | 2.3 Percent reduction |
p-value: 0.195cLDA