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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00908011
• Other study ID #: H08-00287
• Status: Completed
• Phase: N/A
• First received: May 21, 2009
• Last updated: November 30, 2015
• Start date: June 2009
• Est. completion date: January 2015

Study information

• Verified date: November 2015
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: January 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Hypercholesterolemia

Intervention

Drug:
• Ezetimibe
10mg/day ezetimibe in addition to ongoing rosuvastatin treatment (10mg/day)- tablet, orally, 10mg/day for 12 weeks
• Rosuvastatin (standard care)
Increased dose of rosuvastatin to 20mg/day

Locations

Country	Name	City	State
Canada	St. Paul's Hospital HIV Immunodeficiency/Metabolic Clinic	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of British Columbia	Merck Frosst-Schering Pharma, G.P.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		3 months from baseline	No
Secondary	Percent Change in Apolipoprotein B, Percent and Absolute Change Total Cholesterol, LDL, HDL, Triglycerides, Apolipoprotein A1, apolipoproteinB/apoliporoteinA1 Ratio and C-reactive Protein		3 months from baseline	No
Secondary	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		3 months from baseline	Yes