Aortocoronary Saphenous Vein Bypass Graft Atherosclerosis Clinical Trial
Official title:
Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: The Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial
Intermediate saphenous vein graft (SVG) lesions are common, have high rates of progression to
severe lesions or occlusion, and are associated with high incidence of adverse clinical
outcomes.
The ALPINE-SVG trial is a randomized-controlled trial of extended-release niacin vs. placebo
in patients with intermediate saphenous vein graft lesions. The main hypothesis of the study
is that compared to placebo, niacin administration will result in reduction in percent
atheroma volume at 12-month follow-up angiography.
This is a phase II, single-center, double-blind trial that will randomize 138 prior CABG
patients with an intermediate SVG lesion (30%-60% angiographic diameter stenosis) on
clinically-indicated coronary angiography, and HDL-C<60 mg/dL to ER-niacin at a dose of
1500-2000 mg daily or matching placebo (containing 50 mg of niacin that can cause flushing
but has no lipid lowering effect) for 12 months. All patients will receive a statin with goal
LDL-C <70 mg/dL. Coronary angiography, intravascular ultrasonography (IVUS), and
intravascular near-infrared intracoronary spectroscopy (NIRS), and optical coherence
tomography (OCT) of the intermediate SVG lesion will be performed at enrollment and after 12
months in each patient, along with exercise stress testing at 1 month and 12 months, B-mode
carotid ultrasound imaging at enrollment and after 6 and 12 months, reactive hyperemia
peripheral arterial tonometry (RH-PAT) at enrollment and after 6 and 12 months, and with
peripheral blood sampling performed at enrollment and at 1, 3, 6, 9 and 12 months, to
determine whether compared to placebo, administration of ER-niacin will result in:
1. Reduction of the percent atheroma volume (PAV) of the intermediate SVG lesion at
12-month follow-up IVUS imaging (primary endpoint)
2. Reduction of total and normalized total intermediate SVG lesion atheroma volume,
reduction of atheroma volume in the most diseased 10-mm subsegment of the target
intermediate lesion, reduction of atheroma volume in the subsegment of the target
intermediate lesion with lipid core plaque by NIRS, reduction of lipid core burden index
as assessed by near-infrared intracoronary spectroscopy, increase in fibrous cap
thickness and reduction in the prevalence and number of microchannels, in the presence
and extent of necrotic lipid pool, plaque rupture, calcification, and thrombus, as
assessed by optical coherence tomography, and reduction of angiographic intermediate SVG
target lesion failure at 12-month follow-up SVG imaging (secondary endpoints)
3. Increased exercise capacity and reduction in ischemia, as assessed by exercise stress
testing between 1 and 12 months (secondary endpoint)
4. Less increase in mean carotid intima-media thickness at 6 and 12 months (secondary
endpoint)
5. Greater increase in natural logarithmic scaled reactive hyperemia index (L_RHI) at 6 and
12 months (secondary endpoint)
6. Greater increase in EPC-CFU/mL of peripheral blood from baseline to 1, 3, 6, and 12
months post enrollment (secondary endpoint)
7. Reduction of major adverse cardiac events (defined as the composite of death, acute
coronary syndrome, or coronary revascularization) during follow-up (secondary endpoint)
;