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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01221402
Other study ID # 10-029
Secondary ID R01HL102442
Status Completed
Phase Phase 2
First received October 14, 2010
Last updated August 14, 2017
Start date October 2010
Est. completion date November 2015

Study information

Verified date August 2017
Source North Texas Veterans Healthcare System
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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)


Recruitment information / eligibility

Status Completed
Enrollment 38
Est. completion date November 2015
Est. primary completion date October 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Age 18 years or greater

2. Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.

3. Undergoing clinically-indicated coronary and SVG angiography

4. Have an intermediate SVG lesion (defined as a lesion 30-60% angiographic diameter stenosis) without previous percutaneous intervention, amenable to examination with IVUS. The lesion should have no thrombus or ulceration and should not be considered responsible for the patient's clinical presentation and referral for graft angiography.

Exclusion Criteria:

1. Known allergy to niacin

2. History of statin-induced myopathy

3. Positive pregnancy test or breast-feeding

4. Coexisting conditions that limit life expectancy to less than 12 months or that could affect a patient's compliance with the protocol

5. Uncontrolled fasting triglyceride levels ( 500 mg/dL)

6. Fasting LDL-C >200 mg/dL

7. Fasting HDL-C >60 mg/dL

8. Poorly controlled diabetes (glycosylated hemoglobin levels 10%)

9. Current active liver disease or hepatic dysfunction

10. AST or ALT > 2x the upper limit of normal

11. Uncontrolled hypothyroidism (Thyroid Stimulating Hormone >1.5 x upper limit of normal [ULN])

12. Unexplained creatine kinase elevations (>3 x ULN)

13. Recent history of acute gout

14. Serum creatinine > 2.5 mg/dL

15. HIV (due to potential anti-retroviral drug-interactions with niacin)

16. Use of high-dose, antioxidant vitamins (vitamins C, E, or beta-carotene) that may interfere with the HDL-raising effect of niacin

17. Severe peripheral arterial disease limiting vascular access

18. Referral for cardiac catheterization by a physician who is an investigator in the present study.

19. Symptoms consistent with moderate or greater severity of congestive heart failure (New York Heart Association - NYHA class III or IV) or whose most recent determination of left ventricular ejection fraction is <25%

20. Uncontrolled hypertension, defined as either a resting diastolic blood pressure of =100 mmHg or a resting systolic blood pressure of =200 mmHg

21. History of allergic reaction to iodine-based contrast agents

22. Significant medical or psychological condition that, in the opinion of the investigator, may compromise the patient's safety or successful participation in the study

Study Design


Related Conditions & MeSH terms

  • Aortocoronary Saphenous Vein Bypass Graft Atherosclerosis
  • Atherosclerosis
  • Intermediate Saphenous Vein Graft Lesions

Intervention

Drug:
extended-release niacin (Niaspan)
Patients will be randomized in a 1:1 ratio to receive extended-release niacin (1500 - 2000 mg per day) or matching placebo that contains 50 mg of crystalline niacin (enough to cause flushing but has no effect on lipid levels).

Locations

Country Name City State
United States VA North Texas Healthcare System Dallas Texas

Sponsors (3)

Lead Sponsor Collaborator
North Texas Veterans Healthcare System National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Guerra A, Rangan BV, Coleman A, Xu H, Kotsia A, Christopoulos G, Sosa A, Chao H, Han H, Abdurrahim G, Roesle M, de Lemos JA, McGuire DK, Packer M, Banerjee S, Brilakis ES. Effect of Extended-Release Niacin on Carotid Intima Media Thickness, Reactive Hyper — View Citation

Kotsia AP, Rangan BV, Christopoulos G, Coleman A, Roesle M, Cipher D, de Lemos JA, McGuire DK, Packer M, Banerjee S, Brilakis ES. Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: Insights from the Atherosclerosis Lesion Progressi — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary change in percent atheroma volume at 12 months intravascular ultrasonography 12 months
Secondary change in total and normalized total intermediate SVG lesion atheroma volume 12 months
Secondary reduction of atheroma volume in the most diseased 10-mm subsegment of the target intermediate lesion 12 months
Secondary reduction of atheroma volume in the subsegment of the target intermediate lesion with lipid core plaque by near-infrared spectroscopy 12 months
Secondary lipid core burden index as assessed by near-infrared intracoronary spectroscopy 12 months
Secondary 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 12 months
Secondary angiographic intermediate SVG target lesion failure 12 month
Secondary exercise capacity and ischemia, as assessed by exercise stress testing 12 months
Secondary carotid intima-media thickness 6 and 12 months
Secondary reactive hyperemia index 12 months
Secondary EPC-CFU/mL of peripheral blood 12 months
Secondary major adverse cardiac events (defined as the composite of death, acute coronary syndrome, or coronary revascularization) 12 months