Ezetimibe in Patients Hypo-responsive to Statins

NCT00965055 | Terminated Phase 3 Results DMC

• 1 other identifier: 090948
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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).

Conditions

High Cholesterol; Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• LDL-C Reduction

  Study was not analyzed as only 2 subjects were enrolled and the study was terminated due to lack of enrollment.

  6 weeks

Secondary Outcomes (1)

• LDL-C Reduction as Well as Changes in TG, HDL, and Non-HDL Cholesterol.

  24 weeks

Study Arms (2)

Atorvastatin

PLACEBO COMPARATOR

Drug: Atorvastatin

Atorvastatin/Ezetimibe

EXPERIMENTAL

Drug: Ezetimibe; Drug: Atorvastatin

Interventions

Ezetimibe DRUG

10 mg

Also known as: Zetia, Lipitor

Atorvastatin/Ezetimibe

Atorvastatin DRUG

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; Atorvastatin/Ezetimibe

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Diego: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UCSD Medical Center in Hillcrest Clinical Trials Facility

San Diego, California, 92103, United States

Location

MeSH Terms

Conditions

Hypercholesterolemia; Coronary Artery Disease

Interventions

Ezetimibe; Atorvastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Limitations and Caveats

Study was not analyzed as only 2 subjects were enrolled and the study was terminated due to lack of enrollment.

Results Point of Contact

• Title: Ori Ben-Yehuda
• Organization: UCSD

obenyehuda@ucsd.edu

9179697273

Study Officials

• Ori Ben-Yehuda, MD

  UCSD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: August 24, 2009
• First Posted: August 25, 2009
• Study Start: September 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2012
• Last Updated: August 21, 2019
• Results First Posted: August 21, 2019

Record last verified: 2019-08

Locations

US (1)