Ezetimibe in Patients Hypo-responsive to Statins

Phase 3

Terminated

• Conditions: High Cholesterol; Coronary Artery Disease
• Interventions: Drug: Atorvastatin; Drug: Ezetimibe

• Registration Number: NCT00965055
• Lead Sponsor: University of California, San Diego

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 Timeline

• Study First Submitted: 2009-08-24
• Study First Submitted QC: 2009-08-24
• Study First Posted: 2009-08-25
• Study Start: 2009-09
• Primary Completion: 2011-09
• Study Completion: 2012-09
• Status Verified: 2019-08
• Results First Submitted: 2019-08-01
• Results First Submitted QC: 2019-08-01
• Last Update Submitted: 2019-08-01
• Results First Posted: 2019-08-21
• Last Update Posted: 2019-08-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atorvastatin	Atorvastatin	-
Atorvastatin/Ezetimibe	Ezetimibe	-
Atorvastatin/Ezetimibe	Atorvastatin	-

Primary Outcome Measures

Name	Time	Method
LDL-C Reduction	6 weeks	Study was not analyzed as only 2 subjects were enrolled and the study was terminated due to lack of enrollment.

Secondary Outcome Measures

Name	Time	Method
LDL-C Reduction as Well as Changes in TG, HDL, and Non-HDL Cholesterol.	24 weeks

Trial Locations

Locations (1)

UCSD Medical Center in Hillcrest Clinical Trials Facility; 🇺🇸 San Diego, California, United States