Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis

NCT ID: NCT00397657

Last Updated: 2009-06-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2009-10-31

Brief Summary

Recent evidence on the use of statin therapy indicates the potential for ultra-low levels of low-density lipoprotein (LDL-C) to provide greater protection from recurrent coronary heart disease (CHD) events. Thus, in August 2005, the guidelines for the treatment of lipid disorders (NCEP ATPIII) were revised to indicate that an LDL-C treatment goal of 70 mg/dL (revised from 100 mg/dL) was optional for patients with known CHD. In these same guidelines, low levels of high-density lipoprotein (HDL-C) are also suggested but not specifically proscribed as a target of therapy. Recently the ARBITER 2 trial has provided the first evidence of the potential of raising HDL-C with extended release niacin when added to statin monotherapy. However, whether this approach would be superior to a strategy in which lower concentrations of LDL-C are targeted is unknown.

The purpose of ARBITER 6 - HALTS is to compare HDL and LDL-focused strategies of lipid treatments for their effects of atherosclerosis. This study is a prospective, randomized, open-label, blinded endpoint trial comparing treatment strategies of either HDL-raising therapies or LDL reduction for dyslipidemia on carotid atherosclerosis. Subjects with known atherosclerotic coronary or vascular disease or otherwise at high cardiovascular risk through the presence of a coronary risk equivalent who are currently being treated with a statin will be eligible. Subjects will be randomly assigned in an allocation-concealed fashion to open label treatment with either Ezetimibe 10 mg/d for additional LDL-lowering OR Extended-release niacin (1 gm/d, titrated to max tolerable dose up to 2 gm/d) for HDL improvement.

The effects of these 2 different strategies of intensified lipid management on atherosclerosis will be assessed by the change in the carotid intima-media thickness, a validated surrogate endpoint. The data will help guide clinicians on the potential benefits of these lipid treatment strategies.

Conditions

Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Extended release niacin

Group Type: ACTIVE_COMPARATOR

extended release niacin

Intervention Type: DRUG

Extended release niacin will be started at 1000mg and titrated to 2000mg once a day

ezetimibe

Intervention Type: DRUG

Ezetimibe 10mg once daily

Ezetimibe

Group Type: ACTIVE_COMPARATOR

ezetimibe

Intervention Type: DRUG

Ezetimibe 10mg once daily

Interventions

extended release niacin

Extended release niacin will be started at 1000mg and titrated to 2000mg once a day

Intervention Type: DRUG

ezetimibe

Ezetimibe 10mg once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female subjects, ≥ 30 years old with either known atherosclerotic coronary or vascular disease OR coronary risk equivalents defined as either:

• diabetes mellitus,
• multiple coronary risk factors with a Framingham Risk Score > 2% per year, or
• an elevated coronary calcium score (> 400 for men, > 200 for women)
• Currently being treated with a statin (Simvastatin 20 mg/d or its equivalent) as monotherapy for treatment of hyperlipidemia
• Recent lipids (within the past 3 months without interval change in the statin regimen) showing both: LDL-C < 100 mg/dL and HDL-C < 50 mg/dL (men) or < 55 mg/dL (women)

Exclusion Criteria

• Current use of or known intolerance to niacin or ezetimibe
• Known history of liver disease (cirrhosis, chronic hepatitis) or abnormal liver associated enzymes, > 3x the upper laboratory reference value
• Enrollment in another drug or device research protocol
• Females who are pregnant, expect to get pregnant during the course of the study, or are breastfeeding

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

Walter Reed Army Medical Center

FED

Sponsor Role: lead

Responsible Party

Medstar Research Institute and Washington Hospital Center, Washington DC

Principal Investigators

Allen J Taylor, MD

Role: PRINCIPAL_INVESTIGATOR

Medstar Research Institute and Washington Hospital Center, Washington DC.

Locations

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Washington Adventist Hospital

Takoma Park, Maryland, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 2004 Dec 7;110(23):3512-7. doi: 10.1161/01.CIR.0000148955.19792.8D. Epub 2004 Nov 10.

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin. 2006 Nov;22(11):2243-50. doi: 10.1185/030079906x148508.

Reference Type: BACKGROUND

PMID: 17076985 (View on PubMed)

Taylor AJ, Villines TC, Stanek EJ. Paradoxical progression of atherosclerosis related to low-density lipoprotein reduction and exposure to ezetimibe. Eur Heart J. 2012 Dec;33(23):2939-45. doi: 10.1093/eurheartj/ehs105. Epub 2012 May 7.

Reference Type: DERIVED

PMID: 22564353 (View on PubMed)

Villines TC, Stanek EJ, Devine PJ, Turco M, Miller M, Weissman NJ, Griffen L, Taylor AJ. The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration. J Am Coll Cardiol. 2010 Jun 15;55(24):2721-6. doi: 10.1016/j.jacc.2010.03.017.

Reference Type: DERIVED

PMID: 20399059 (View on PubMed)

Taylor AJ, Villines TC, Stanek EJ, Devine PJ, Griffen L, Miller M, Weissman NJ, Turco M. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009 Nov 26;361(22):2113-22. doi: 10.1056/NEJMoa0907569. Epub 2009 Nov 15.

Reference Type: DERIVED

PMID: 19915217 (View on PubMed)

Other Identifiers

06-12027

Identifier Type: -

Identifier Source: org_study_id