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

June 16, 2009 updated by: Walter Reed Army Medical Center

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20307
        • Walter Reed Army Medical Center
    • Maryland
      • Takoma Park, Maryland, United States, 20912
        • Washington Adventist Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ezetimibe
Drug: ezetimibe
Ezetimibe 10mg once daily
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoint is the change in carotid intima-media thickness between groups after 14 months
Time Frame: 14 months
14 months

Secondary Outcome Measures

Outcome Measure
Time Frame
The change in lipid values and lipid subfractions
Time Frame: 14 months
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)
Time Frame: 14 months
14 months
Drug discontinuation due to adverse effects
Time Frame: 14 months
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
Time Frame: 14 months
14 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Walter Reed Army Medical Center

Collaborators

Abbott

Investigators

  • Principal Investigator: Allen J Taylor, MD, Medstar Research Institute and Washington Hospital Center, Washington DC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Anticipated)

August 1, 2009

Study Completion (Anticipated)

October 1, 2009

Study Registration Dates

First Submitted

November 8, 2006

First Submitted That Met QC Criteria

November 8, 2006

First Posted (Estimate)

November 9, 2006

Study Record Updates

Last Update Posted (Estimate)

June 17, 2009

Last Update Submitted That Met QC Criteria

June 16, 2009

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-12027

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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