Clinical trial NCT00965055: Ezetimibe in Patients Hypo-responsive to Statins
Official title: Atorvastatin vs. Atorvastatin/Ezetimibe in Patients With Hypo-response to Initial Dose Statin Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: High Cholesterol
Coronary Artery Disease
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2009-08-25
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: LDL-C Reduction
timeFrame: 6 weeks
Secondary outcomes:
measure: LDL-C Reduction as Well as Changes in TG, HDL, and Non-HDL Cholesterol.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Medical Center in Hillcrest Clinical Trials Facility
state: California
Study officials:
affiliation: UCSD
name: Ori Ben-Yehuda, MD
role: PRINCIPAL_INVESTIGATOR
References: