Ezetimibe in Patients Hypo-responsive to Statins

This study has been terminated.
(The study was terminated due to inability to recruit subjects. A total of 2/100 anticipated were radomized.)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Ori Ben-Yehuda, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00965055
First received: August 24, 2009
Last updated: January 25, 2013
Last verified: January 2013
  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

Resource links provided by NLM:


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 ]

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:
  • 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


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
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Sharp & Dohme Corp.
Investigators
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
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 02, 2014