Ezetimibe in Patients Hypo-responsive to Statins
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Purpose
Response to statin therapy for elevated low density lipoprotein is variable and may be influenced by cholesterol absorption. This study will evaluate whether combination therapy with atorvastatin/ezetimibe will be superior to atorvastatin alone in subjects who have less than 25% LDL reduction on starting dose statin (eg, atorvastatin 10 mg daily or simvastatin 20 mg daily).
| Condition | Intervention | Phase |
|---|---|---|
|
High Cholesterol Coronary Artery Disease |
Drug: Ezetimibe Drug: Atorvastatin |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Atorvastatin vs. Atorvastatin/Ezetimibe in Patients With Hypo-response to Initial Dose Statin Therapy |
- LDL-C reduction [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
- LDL-C reduction as well as changes in TG, HDL, and non-HDL Cholesterol. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
| Enrollment: | 2 |
| Study Start Date: | September 2009 |
| Study Completion Date: | September 2012 |
| Primary Completion Date: | September 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Placebo Comparator: Atorvastatin |
Drug: Atorvastatin
Visit 1: (atorvastatin open label challenge): Those who complete the initial screening and washout period will receive open label atorvastatin 10 mg daily for 6 weeks to verify compliance and confirm hyporesponse to statin therapy. Visit 2: After 6 weeks of therapy repeat baseline fasting cholesterol. Those with LDL-c reduction of 25% or less will be able to proceed to next phase. Patients with greater than 25% LDL-C reduction will be excluded. We expect to randomize 80 patients Visit 2a: Dispensing of first randomized drug allocation- all patients receive open label atorvastatin 10 mg with additional ezetimibe 10 mg or matching placebo. No blood test during this visit. Visit 3, 4, 5: Dose titration to atorvastatin to 20 mg, 40 mg, 80 mg, respectively, after fasting blood test Blood collected in visits 3, 4, and 5 will be stored for additional tests regarding cholesterol metabolism and inflammation. Visit 6: Final cholesterol panel and conclusion of study period |
| Experimental: Atorvastatin/Ezetimibe |
Drug: Ezetimibe
10 mg
Other Names:
Drug: Atorvastatin
Visit 1: (atorvastatin open label challenge): Those who complete the initial screening and washout period will receive open label atorvastatin 10 mg daily for 6 weeks to verify compliance and confirm hyporesponse to statin therapy. Visit 2: After 6 weeks of therapy repeat baseline fasting cholesterol. Those with LDL-c reduction of 25% or less will be able to proceed to next phase. Patients with greater than 25% LDL-C reduction will be excluded. We expect to randomize 80 patients Visit 2a: Dispensing of first randomized drug allocation- all patients receive open label atorvastatin 10 mg with additional ezetimibe 10 mg or matching placebo. No blood test during this visit. Visit 3, 4, 5: Dose titration to atorvastatin to 20 mg, 40 mg, 80 mg, respectively, after fasting blood test Blood collected in visits 3, 4, and 5 will be stored for additional tests regarding cholesterol metabolism and inflammation. Visit 6: Final cholesterol panel and conclusion of study period |
Detailed Description:
Specific Aim 1 To identify a patient population seen in the University of California, San Diego general internal medicine and cardiology subspecialty clinics as well as referrals from community physicians who are hyporesponsive to statin therapy (defined as an initial LDL reduction of <25% in response to 10mg of atorvastatin or 20mg of simvastatin- expected mean reduction is 35% -37% for starting dose simvastatin and atorvastatin).
Specific Aim 2 To test the hypothesis, with a prospective study, that a hyporesponse to statin therapy may be related to increased cholesterol absorption, and that this hyporesponse may be overcome by the addition of ezetimibe, a specific cholesterol absorption inhibitor.
Specific Aim 3 To evaluate whether patients with less than 25% LDL reduction on 10 mg of atorvastatin (or 20 mg of simvastatin) would achieve significantly greater LDL reduction with combination therapy (atorvastatin/ezetimibe) than with statin dose titration (using atorvastatin).
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients will need to have an LDL-C level of 130 mg/dl or greater without treatment.
- They must have demonstrated an initial LDL-C reduction of less than 25% on 10 mg of atorvastatin or 20 mg of simvastatin.
- Eligible patients will be those deemed by their physicians to be eligible for lipid lowering therapy with a statin and to have stable CAD, CAD equivalent per NCEP guidelines, or Framingham risk of 10-20%.
Exclusion Criteria:
- Recent (<3 months) diagnosis of Acute Coronary Syndromes due to ethical considerations [10].
- Pregnant patients, those planning to become pregnant, or those who are breast feeding, those with liver disease, history allergic reaction to any agent used in the trial, history of myositis, myopathy, pancreatitis, hypertriglyceridemia (TG > 400 mg/dL), history of significant alcohol or drug abuse, history of organ transplantation, or patient refusal.
Contacts and Locations| United States, California | |
| UCSD Medical Center in Hillcrest Clinical Trials Facility | |
| San Diego, California, United States, 92103 | |
| Principal Investigator: | Ori Ben-Yehuda, MD | UCSD |
More Information
No publications provided
| Responsible Party: | Ori Ben-Yehuda, Professor of Medicine, University of California, San Diego |
| ClinicalTrials.gov Identifier: | NCT00965055 History of Changes |
| Other Study ID Numbers: | 090948 |
| Study First Received: | August 24, 2009 |
| Last Updated: | January 25, 2013 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Coronary Artery Disease Myocardial Ischemia Coronary Disease Hypercholesterolemia Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders |
Metabolic Diseases Atorvastatin Ezetimibe Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Enzyme Inhibitors Lipid Regulating Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 19, 2013