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

Sponsor

Walter Reed Army Medical Center (U.S. Fed)

Overall Status

Terminated

CT.gov ID

NCT00397657

Collaborator

Abbott (Industry)

400

Enrollment

Locations

Arms

Duration (Months)

200

Patients Per Site

5.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: extended release niacin Drug: ezetimibe	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

ARBITER 6: ARterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6 - HDL and LDL Treatment Strategies in Atherosclerosis (HALTS)

Study Start Date :

Nov 1, 2006

Anticipated Primary Completion Date :

Aug 1, 2009

Anticipated Study Completion Date :

Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Extended release niacin	Drug: extended release niacin Extended release niacin will be started at 1000mg and titrated to 2000mg once a day Drug: ezetimibe Ezetimibe 10mg once daily
Active Comparator: Ezetimibe	Drug: ezetimibe Ezetimibe 10mg once daily

Arm

Intervention/Treatment

Active Comparator: Extended release niacin

Drug: extended release niacin

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

Drug: ezetimibe

Ezetimibe 10mg once daily

Active Comparator: Ezetimibe

Drug: ezetimibe

Ezetimibe 10mg once daily

Outcome Measures

Primary Outcome Measures

The primary endpoint is the change in carotid intima-media thickness between groups after 14 months [14 months]

Secondary Outcome Measures

The change in lipid values and lipid subfractions [14 months]
A composite endpoint consisting of all major adverse cardiovascular events (coronary heart disease death, myocardial infarction, myocardial revascularization, admission to the hospital for an acute coronary syndrome) [14 months]
Drug discontinuation due to adverse effects [14 months]
Quality of life measured with the EQ-5D questionnaire- a generic questionnaire for describing and valuing subjects' health-related quality of life that has been studied in cardiovascular subjects [14 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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