Ezetimibe in Patients Hypo-responsive to Statins - Full Text View

Sponsor:	University of California, San Diego
Collaborator:	Merck
Information provided by:	University of California, San Diego
ClinicalTrials.gov Identifier:	NCT00965055

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Atorvastatin vs. Atorvastatin/Ezetimibe in Patients With Hypo-response to Initial Dose Statin Therapy

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol Coronary Artery Disease Statins

Drug Information available for: Atorvastatin Atorvastatin calcium Ezetimibe

U.S. FDA Resources

Further study details as provided by University of California, San Diego:

Primary Outcome Measures:

LDL-C reduction [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

LDL-C reduction as well as changes in TG, HDL, and non-HDL Cholesterol. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	September 2009
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Atorvastatin: Placebo Comparator	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
Atorvastatin/Ezetimibe: Experimental	Drug: Ezetimibe 10 mg 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

Arms

Assigned Interventions

Atorvastatin: Placebo Comparator

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

Atorvastatin/Ezetimibe: Experimental

Drug: Ezetimibe

10 mg

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 UCSD 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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00965055

Locations

United States, California
UCSD Medical Center in Hillcrest Clinical Trials Facility
San Diego, California, United States, 92103

Sponsors and Collaborators

University of California, San Diego

Merck

Investigators

Principal Investigator:

Ori Ben-Yehuda, MD

UCSD

More Information

No publications provided

Responsible Party:	UCSD ( Ori Ben-Yehuda, MD )
Study ID Numbers:	090948
Study First Received:	August 24, 2009
Last Updated:	August 24, 2009
ClinicalTrials.gov Identifier:	NCT00965055 History of Changes
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Arterial Occlusive Diseases
Antimetabolites
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Myocardial Ischemia
Antilipemic Agents
Vascular Diseases
Enzyme Inhibitors
Ezetimibe

Arteriosclerosis
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Coronary Disease
Therapeutic Uses
Cardiovascular Diseases
Coronary Artery Disease
Atorvastatin

ClinicalTrials.gov processed this record on February 08, 2010