Addition of Ezetimibe (Ezetrol®) to Ongoing Therapy With Rosuvastatin (Crestor®) in HIV Positive Patients Not Reaching Cholesterol Targets

• ClinicalTrials.gov Identifier: NCT00908011
• Recruitment Status: Completed
• First Posted: May 25, 2009
• Results First Posted: January 1, 2016
• Last Update Posted: January 1, 2016
• Sponsor: University of British Columbia
• Collaborator: Merck Frosst-Schering Pharma, G.P.
• Information provided by (Responsible Party): University of British Columbia

Study Description

Brief Summary:

This study involves comparing the effectiveness of treatments in HIV positive patients who may be predisposed to heart attack or stroke. The investigators will evaluate the effectiveness of two drugs, often prescribed by doctors to these patients, at lowering cholesterol and thereby making the patient less them less vulnerable to suffering a heart attack or stroke. The investigators believe that the addition of a second drug, from a different class of cholesterol lowering medications, will improve the outcome of the patients by lowering cholesterol.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia; HIV Infections	Drug: Ezetimibe; Drug: Rosuvastatin (standard care)	Not Applicable

Detailed Description:

This study seeks to determine whether HIV positive patients who have suboptimal lipids and/or are not reaching specified lipid targets will benefit from the addition of a second lipid lowering drug (ezetimibe) to existing lipid lowering therapy with a statin (specifically rosuvastatin) versus increasing the dose of the ongoing statin in terms of improvements in serum lipid parameters namely total cholesterol, LDL, HDL, triglycerides and apolipoprotein B100 (apoB), apolipoprotein A1 (apoA1), apoB/apoA1 ratio.

The target population will be HIV+ patients with hypercholesterolemia due to highly active antiretroviral therapy, the study will have a randomized, parallel design. Sample size will be 50 patients already taking 10 mg of rosuvastatin who are not reaching lipid targets to receive either an increased dose of rosuvastatin (20mg) or to receive 10mg ezetimibe in addition to their ongoing rosuvastatin therapy. There will be 25 patients randomized to each group.

At baseline serum samples will be obtained and tested for serum triglycerides, total cholesterol, HDL, total cholesterol:HDL ratio, apoB, apoA1, apoB/apoA1 ratio, liver transaminases (AST and ALT), CK, thyroid stimulating hormone, creatinine and fasting blood glucose.

After 12 weeks of therapy serum samples will once again be obtained and tested for serum triglycerides, total cholesterol, HDL, total cholesterol:HDL ratio, apolipoprotein B100, liver transaminases (AST and ALT), CK, thyroid stimulating hormone, creatinine and fasting blood glucose.

The primary hypothesis is that the combination of rosuvastatin and ezetimibe will lower serum apolipoprotein B100/apolipoprotein A1 ratio more so than an increased dose of rosuvastatin alone, in participants with mixed dyslipidemia associated with HIV therapy.

Secondarily we believe the combination of rosuvastatin and ezetimibe will lower the concentrations of serum cholesterol, LDL-cholesterol, triglycerides, apolipoprotein B100 and C-reactive protein more so than an increased dose of rosuvastatin alone, and that there will be no increase in side effects when administered to participants with mixed dyslipidemia associated with HIV therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized Study to Determine the Effect of Ezetimibe in Addition to Rosuvastatin on Lipids in Participants With the Hypercholesterolemia Associated With HIV Antiretroviral Therapy
• Study Start Date: June 2009
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: January 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Ezetimibe; 10mg/day ezetimibe in addition to ongoing rosuvastatin treatment (10mg/day)	Drug: Ezetimibe; 10mg/day ezetimibe in addition to ongoing rosuvastatin treatment (10mg/day)- tablet, orally, 10mg/day for 12 weeks; Other Name: Ezetrol
Active Comparator: Standard Care; Increased dose of rosuvastatin to 20mg/day	Drug: Rosuvastatin (standard care); Increased dose of rosuvastatin to 20mg/day; Other Name: Crestor

Outcome Measures

Primary Outcome Measures :

1. The Primary Endpoint is the Difference in Final Value of Serum Apolipoprotein B Between Participants Treated With Rosuvastatin Versus Participants Treated With Both Rosuvastatin and Ezetimibe. [ Time Frame: 3 months from baseline ]

Secondary Outcome Measures :

1. Percent Change in Apolipoprotein B, Percent and Absolute Change Total Cholesterol, LDL, HDL, Triglycerides, Apolipoprotein A1, apolipoproteinB/apoliporoteinA1 Ratio and C-reactive Protein [ Time Frame: 3 months from baseline ]
2. Assessment of Safety Parameters, Specifically Incidence of Complications as Measured by an Increase in AST &/or ALT ≥3-fold ULN & a CK ≥10-fold ULN [ Time Frame: 3 months from baseline ]

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• HIV positive
• currently taking 10mg of rosuvastatin
• recent (within three months) fasting lipid profile in which the serum total cholesterol to HDL ratio is >5.0

Exclusion Criteria:

• Previous adverse reaction to ezetimibe
• taken ezetimibe within 30 days of starting the study
• history of vascular disease
• allergic reaction or muscle problems while taking any statin
• currently taking other lipid lowering medications (i.e. a fibrates or cholestyramine)

Contacts and Locations

Locations

Canada, British Columbia

St. Paul's Hospital HIV Immunodeficiency/Metabolic Clinic

Vancouver, British Columbia, Canada, V6Z 1Y6

Sponsors and Collaborators

University of British Columbia

Merck Frosst-Schering Pharma, G.P.

Investigators

• Principal Investigator: Greg Bondy, MD; University of British Columbia

More Information

• Responsible Party: University of British Columbia
• ClinicalTrials.gov Identifier: NCT00908011
• Other Study ID Numbers: H08-00287
• First Posted: May 25, 2009
• Results First Posted: January 1, 2016
• Last Update Posted: January 1, 2016
• Last Verified: November 2015

Keywords provided by University of British Columbia:

Hypercholesterolemia; HIV; Ezetimibe; Statin; Apolipoprotein B100/Apolipoprotein A1 ratio

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Rosuvastatin Calcium; Ezetimibe; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors