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

This study has been terminated.
(Independent steering committee has stopped the trial based on results of a prespecified, blinded interim analysis. It was not stopped due to safety concerns.)
Sponsor:
Collaborator:
Abbott
Information provided by:
Walter Reed Army Medical Center
ClinicalTrials.gov Identifier:
NCT00397657
First received: November 8, 2006
Last updated: June 16, 2009
Last verified: June 2009
  Purpose

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 Intervention Phase
Atherosclerosis
Drug: extended release niacin
Drug: ezetimibe
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Walter Reed Army Medical Center:

Primary Outcome Measures:
  • The primary endpoint is the change in carotid intima-media thickness between groups after 14 months [ Time Frame: 14 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change in lipid values and lipid subfractions [ Time Frame: 14 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Drug discontinuation due to adverse effects [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: November 2006
Estimated Study Completion Date: October 2009
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00397657

Locations
United States, District of Columbia
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307
United States, Maryland
Washington Adventist Hospital
Takoma Park, Maryland, United States, 20912
Sponsors and Collaborators
Walter Reed Army Medical Center
Abbott
Investigators
Principal Investigator: Allen J Taylor, MD Medstar Research Institute and Washington Hospital Center, Washington DC.
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Allen J Taylor, MD, Medstar Research Institute and Washington Hospital Center, Washington DC
ClinicalTrials.gov Identifier: NCT00397657     History of Changes
Other Study ID Numbers: 06-12027
Study First Received: November 8, 2006
Last Updated: June 16, 2009
Health Authority: United States: Federal Government

Keywords provided by Walter Reed Army Medical Center:
carotid intima media thickness
atherosclerosis
niacin
coronary heart disease
HDL-C
LDL-C

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Niacin
Ezetimibe
Nicotinic Acids
Niacinamide
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anticholesteremic Agents

ClinicalTrials.gov processed this record on September 15, 2014