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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by University of British Columbia.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Merck Frosst-Schering Pharma, G.P.
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT00908011
First received: May 21, 2009
Last updated: November 21, 2011
Last verified: November 2011
  Purpose

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 Intervention
Hypercholesterolemia
HIV Infections
Drug: Ezetimibe
Drug: Rosuvastatin (standard care)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: June 2009
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
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
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: NCT00908011

Contacts
Contact: Kevin Johns (604) 682-2344 ext 63139 kevinwjohns@gmail.com

Locations
Canada, British Columbia
St. Paul's Hospital HIV Immunodeficiency/Metabolic Clinic Recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Kevin Johns    (604) 682-2344 ext 63139    kevinwjohns@gmail.com   
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

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT00908011     History of Changes
Other Study ID Numbers: H08-00287
Study First Received: May 21, 2009
Last Updated: November 21, 2011
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
Hypercholesterolemia
HIV
Ezetimibe
Statin
Apolipoprotein B100/Apolipoprotein A1 ratio

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hypercholesterolemia
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Rosuvastatin
Ezetimibe
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 26, 2014