Ezetimibe in Patients Hypo-responsive to Statins

Tracking Information
First Submitted Date ICMJE	August 24, 2009
First Posted Date ICMJE	August 25, 2009
Last Update Posted Date	January 28, 2013
Study Start Date ICMJE	September 2009
Actual Primary Completion Date	September 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 24, 2009)	LDL-C reduction [ Time Frame: 6 weeks ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00965055 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: August 24, 2009)	LDL-C reduction as well as changes in TG, HDL, and non-HDL Cholesterol. [ Time Frame: 24 weeks ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Ezetimibe in Patients Hypo-responsive to Statins
Official Title ICMJE	Atorvastatin vs. Atorvastatin/Ezetimibe in Patients With Hypo-response to Initial Dose Statin Therapy
Brief Summary	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).
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).
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	High Cholesterol; Coronary Artery Disease
Intervention ICMJE	Drug: Ezetimibe 10 mg Other Names: Zetia Lipitor; 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
Study Arms	Placebo Comparator: Atorvastatin Intervention: Drug: Atorvastatin; Experimental: Atorvastatin/Ezetimibe Interventions: Drug: Ezetimibe Drug: Atorvastatin
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: January 25, 2013)	2
Original Estimated Enrollment ICMJE; (submitted: August 24, 2009)	100
Actual Study Completion Date	September 2012
Actual Primary Completion Date	September 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 80 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00965055
Other Study ID Numbers ICMJE	090948
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Ori Ben-Yehuda, University of California, San Diego
Study Sponsor ICMJE	University of California, San Diego
Collaborators ICMJE	Merck Sharp & Dohme Corp.
Investigators ICMJE	Principal Investigator: Ori Ben-Yehuda, MD UCSD
PRS Account	University of California, San Diego
Verification Date	January 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP