A Prospective, Open Label Comparison of Ezetimibe, Niacin, and Colestipol as Adjunct Therapy in Lipid Reduction

Study Overview
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Brief Summary
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To compare LDL reduction compared to baseline in patients using maximum tolerated HMG CoA Reductase inhibitor (statin) therapy with adjunctive therapy with ezetimibe, colestipol, or niacin. The patient's cardiovascular risks are assessed to determine if National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III) guidelines for low density lipoprotein (LDL) reduction were achieved between the three groups. Secondary measures examine the safety issues with liver function test (LFT) monitoring and rhabdomyolysis. High-density lipoproteins (HDL) elevations are monitored between the three groups to determine efficacy as a secondary outcome.

Detailed Description
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: Patients with hyperlipidemia who sign consent and who are currently at maximum tolerated dose of a statin and are not meeting NCEP ATPIII treatment goals for LDL cholesterol are enrolled in 12-week open label, prospective trial. Patients are randomized into one of three groups to receive ezetimibe, niacin, or colestipol in addition to current statin therapy. Patients are titrated as tolerated to therapeutic doses of study medications (ezetimibe 10mg/day, niacin 1500mg/day, and colestipol 20gm/day). At baseline, informed consent; a laboratory admission profile (Chem20); weight; height; blood pressure; concomitant medications; cholesterol medication history; and grapefruit juice consumption data are gathered. At weeks 6 and 12, patients have their cholesterol panels and liver function tests assessed. Patients are also interviewed regarding side effects (including rhabdomyolysis), tolerance, changes in concomitant medications, and grapefruit juice consumption, along with weight and blood pressure measurements.

Official Title
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A Prospective, Open Label Comparison of Ezetimibe, Niacin, and Colestipol as Adjunct Therapy in Lipid Reduction

Conditions
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Hyperlipidemia, Hypercholesterolemia

Intervention / Treatment
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* Drug: Niacin
* Drug: Colestipol
* Drug: Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veterans eligible for treatment at the Tuscaloosa VA Medical Center 50 years of age Male or female Any race or ethnic group Signed informed consent Hyperlipidemia despite current maximum tolerated dose of an HMG CoA Reductase inhibitor (statin) for > 6 weeks Currently not meeting NCEP ATPIII treatment goals for LDL cholesterol Exclusion Criteria: Known hypersensitivity or intolerance to ezetimibe, niacin, or colestipol Previous failed adequate trial of adjunctive ezetimibe, niacin, or colestipol Consumes more than 8oz. grapefruit juice daily Significant medical condition that would impact safety evaluations (i.e. significantly elevated LFT, hepatitis, severe dermatitis, uncontrolled diabetes, severe GI disease, fibromyalgia, renal failure, recent CVA or MI, pancreatitis, etc.) Receiving medications that would be contraindicated to use in combination with ezetimibe, niacin, or colestipol

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Statin with Niacin<br>Niacin dose range of 500-1500mg (average 888mg) | Drug: Niacin<br> <br> |
| Active Comparator: Statin with Colestipol<br>Colestipol dose range 5-15gm (average 9.5gm) | Drug: Colestipol<br> <br> |
| Active Comparator: Statin with Ezitimibe<br>Ezitimibe 10mg (average 10mg) | Drug: Ezetimibe<br> <br> * Other names: Zetia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL Goal Attainment | Each participant had his LDL goal calculated based on the NCEP ATPIII guidelines. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LFT Elevation |  | 12 weeks | 
| Incidents of Rhabdomyolysis |  | 12 weeks | 
| Change in HDL From Baseline to 12 Weeks. |  | baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ezetimibe, niacin, colestipol, hyperlipidemia, adjunct therapy, zetia