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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

August 24, 2009
January 25, 2013
September 2009
September 2011   (final data collection date for primary outcome measure)
LDL-C reduction [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00965055 on ClinicalTrials.gov Archive Site
LDL-C reduction as well as changes in TG, HDL, and non-HDL Cholesterol. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Ezetimibe in Patients Hypo-responsive to Statins
Atorvastatin vs. Atorvastatin/Ezetimibe in Patients With Hypo-response to Initial Dose Statin Therapy

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).

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).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • High Cholesterol
  • Coronary Artery Disease
  • 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

  • Placebo Comparator: Atorvastatin
    Intervention: Drug: Atorvastatin
  • Experimental: Atorvastatin/Ezetimibe
    Interventions:
    • Drug: Ezetimibe
    • Drug: Atorvastatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
2
September 2012
September 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00965055
090948
Yes
Ori Ben-Yehuda, University of California, San Diego
University of California, San Diego
Merck Sharp & Dohme Corp.
Principal Investigator: Ori Ben-Yehuda, MD UCSD
University of California, San Diego
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP