Acute Coronary Syndrome
Conditions
Keywords
Atherosclerosis
Brief summary
The purpose of this study is to determine the effect of VIA-2291 as compared to placebo on vascular inflammation following 24 weeks of dosing.
Detailed description
The effect of VIA-2291 on vascular inflammation will be assessed through 18FDG PET vascular imaging measurements and various biomarkers after 24 weeks.
Interventions
DRUGVIA-2291
100 mg, oral dosing, 1 time daily for 24 weeks
DRUGPlacebo
oral dosing, 1 time daily for 24 weeks
Sponsors
Massachusetts General Hospital
Icahn School of Medicine at Mount Sinai
University of Massachusetts, Worcester
Winthrop University Hospital
Montreal Heart Institute
Tallikut Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Female patients must be of non-childbearing potential * Recent acute coronary syndrome \[(ACS) ST elevation myocardial infarction (STEMI), non-STEMI or unstable angina) event documented by ECG, cardiac enzymes or angiogram\] 1 - 3 months prior to randomization * Carotid or ascending aorta artery plaque inflammation Target-to-Background Ratio (TBR) ≥ 1.6 * Receiving concomitant statin therapy following the qualifying ACS event for a minimum of 4 weeks, including a stable statin dose regimen for 2 weeks prior to randomization.
Exclusion criteria
* Renal insufficiency defined as creatinine \>1.5 x upper limit of normal (ULN) * Cirrhosis, recent hepatitis, alanine aminotransferase (ALT) \>1.5 x ULN (i.e., above the normal range) or positive screening test for hepatitis B (hepatitis B surface antigen) or hepatitis C (by ELISA) * Type I diabetes and uncontrolled Type 2 diabetes defined as hemoglobin A1c (HbA1c) \> 9% * Heart failure defined by New York Heart Association Class III or IV * Coronary Artery Bypass Surgery (CABG) within 4 months of randomization * Use of zileuton, montelukast, coumadin or steroids * Acetaminophen use in any form in the 7 days before enrollment at Visit 1 * Allergy to contrast agents * Planned additional cardiac intervention (e.g., PCI, CABG) within next 6 months * Current atrial fibrillation, atrial flutter or frequent premature ventricular contractions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plaque Imaging After 24 Weeks | Baseline and 24 Weeks | To evaluate the effect of VIA-2291 100 mg relative to placebo on the change from baseline in the target (plaque) to background (blood) ratio (TBR) from an index vessel (either right carotid, left carotid or ascending aorta) based on the standardized 18fluorodeoxy glucose (FDG) uptake measured with PET in patients with acute coronary syndrome and vascular inflammation after 24 weeks of daily dosing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plaque Imaging After 6 Weeks | Baseline and 6 Weeks | To evaluate the effect of VIA-2291 100 mg relative to placebo on the change from baseline in the TBR from an index vessel (either right carotid, left carotid or ascending aorta) based on the standardized 18FDG uptake measured with PET in patients after 6 weeks of daily dosing. |
Countries
United States
Participant flow
Recruitment details
Patients were screened between November 2007 and April 2009
Pre-assignment details
Subjects had Acute Coronory Syndrome (ACS) 1-3 months prior to randomization and must have received concomitant statin therapy for a minimum of 4 weeks and had a stable statin dose regimen for 2 weeks prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| VIA-2291 VIA-2291 100mg | 26 |
| Placebo Matching placebo | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Subject returned to home country | 0 | 1 |
| Overall Study | Withdrawal of consent | 0 | 1 |
Baseline characteristics
| Characteristic | VIA-2291 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 7 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 19 Participants | 40 Participants |
| Age Continuous | 56.2 years STANDARD_DEVIATION 9.5 | 58.7 years STANDARD_DEVIATION 8 | 57.4 years STANDARD_DEVIATION 8.79 |
| Region of Enrollment Canada | 11 participants | 10 participants | 21 participants |
| Region of Enrollment United States | 15 participants | 16 participants | 31 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 24 Participants | 22 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 26 | 17 / 26 |
| serious Total, serious adverse events | 5 / 26 | 5 / 26 |
Outcome results
Primary
Change From Baseline in Plaque Imaging After 24 Weeks
To evaluate the effect of VIA-2291 100 mg relative to placebo on the change from baseline in the target (plaque) to background (blood) ratio (TBR) from an index vessel (either right carotid, left carotid or ascending aorta) based on the standardized 18fluorodeoxy glucose (FDG) uptake measured with PET in patients with acute coronary syndrome and vascular inflammation after 24 weeks of daily dosing.
Time frame: Baseline and 24 Weeks
Population: Evaluable Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VIA-2291 | Change From Baseline in Plaque Imaging After 24 Weeks | -0.01 TBR | 95% Confidence Interval 11.19 |
| Placebo | Change From Baseline in Plaque Imaging After 24 Weeks | -0.06 TBR | 95% Confidence Interval 11.92 |
Comparison: ANCOVA model adjusted for baseline valuep-value: 0.34ANCOVA
Secondary
Change From Baseline in Plaque Imaging After 6 Weeks
To evaluate the effect of VIA-2291 100 mg relative to placebo on the change from baseline in the TBR from an index vessel (either right carotid, left carotid or ascending aorta) based on the standardized 18FDG uptake measured with PET in patients after 6 weeks of daily dosing.
Time frame: Baseline and 6 Weeks
Population: Evaluable Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VIA-2291 | Change From Baseline in Plaque Imaging After 6 Weeks | 0.01 TBR | 95% Confidence Interval 8.37 |
| Placebo | Change From Baseline in Plaque Imaging After 6 Weeks | -0.07 TBR | 95% Confidence Interval 9.5 |
Comparison: ANCOVA model adjusted for baselinep-value: 0.15ANCOVA