Safety, Effectiveness, and Tolerability of Ezetimibe Combined With Statins for the Treatment of High Cholesterol in HIV Infected Adults

HIV Infections Clinical Trial

Official title:

A Pilot Study of the Safety, Efficacy, and Tolerability of Ezetimibe (Zetia) in Combination With Statin Therapy for the Treatment of Elevated LDL Cholesterol in HIV-Infected Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00099684
• Other study ID #: ACTG A5209
• Status: Completed
• Phase: N/A
• First received: December 17, 2004
• Last updated: October 26, 2012
• Start date: November 2005
• Est. completion date: May 2007

Study information

• Verified date: October 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Anti-HIV drugs, especially protease inhibitors (PIs), have been linked to lipid metabolism problems, including elevations in low density lipoprotein cholesterol (LDL-c), triglycerides, and total cholesterol. Ezetimibe is a lipid-controlling drug; statins are part of another class of lipid-lowering drugs popularly prescribed to people with high cholesterol. The purpose of this study is to determine the safety, effectiveness, and tolerability of ezetimibe in combination with statin therapy in adults who are taking anti-HIV drugs and have high cholesterol.

Study hypothesis: In HIV infected adults, ezetimibe in combination with statin therapy will result in significantly lower LDL-c compared to statin therapy alone.

Description:

Lipid metabolism abnormalities are common complications of HIV therapy, particularly with PIs. Statins and other lipid-lowering agents are often prescribed to control elevated cholesterol levels in both HIV infected and uninfected people. However, both antiretroviral therapy (ART) and lipid-lowering drugs may be associated with cardiovascular disease, so there is a clear need to find a lipid-lowering drug with low toxicity. This study will evaluate the safety, efficacy, and tolerability of ezetimibe, a lipid-controlling agent, in combination with ongoing statin therapy in HIV infected people currently on ART.

This study will last 28 weeks. All participants will be required to continue their current stable statin therapy and ART for the duration of the study.

Participants will be randomly assigned to one of two arms. Arm 1 participants will receive ezetimibe daily for 12 weeks, no treatment for 4 weeks, then placebo daily for 12 weeks. Arm 2 participants will receive placebo daily for 12 weeks, no treatment for 4 weeks, and then ezetimibe daily for 12 weeks. There will be 9 study visits; they will occur at study screening, at study entry, and every 4 weeks thereafter. Clinical assessment and blood collection will occur at all visits. Participants will be asked to complete an adherence questionnaire at Weeks 4, 12, 20, and 28, and will also be encouraged to coenroll in ACTG A5128 (Consent for Use of Stored Patient Specimens for Future Testing).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV infected

• On ART for at least 3 months prior to study entry, and on stable ART for at least 30 days prior to study entry

• Taking one of the study-recommended statins for at least 3 months prior to study entry, and on stable statin therapy for at least 30 days immediately prior to study entry

• On lipid-lowering diet and exercise program for at least 30 days prior to screening, and willing to continue both for the duration of the study

• LDL-c of 130 mg/dL or greater within 30 days prior to study entry

• Willing to use acceptable forms of contraception

• If on hormone replacement therapy, must be on a stable dose or dose-equivalent therapy for at least 30 days prior to study entry, and must be willing to continue the same dose for the duration of the study. People taking physiologic testosterone replacement therapy are not excluded.

• If taking oral contraceptives, must be on a stable dose or dose-equivalent therapy for at least 30 days prior to study entry, and must be willing to continue the same dose for the duration of the study

Exclusion Criteria:

• Active cancer or new diagnosis of cancer within the last 5 years. People with skin cancers, including Kaposi's sarcoma, that do not require systemic treatment are not excluded.

• Prior use of ezetimibe

• Known allergy or sensitivity to ezetimibe or its components

• Diabetes mellitus or use of any diabetic medications within 30 days prior to study entry

• History of coronary heart disease

• History of or current congestive heart failure (New York Heart Association Class III or IV)

• Known atherosclerotic disease risk (e.g., history of myocardial infection, bypass surgery, angioplasty, angina pectoris with a positive stress test or angiographic documentation)

• Vascular abnormalities (e.g., cerebrovascular disease, peripheral vascular disease, abdominal aortic aneurysm, or leg artery blockages)

• Untreated or uncontrolled hypothyroidism

• Current drug or alcohol abuse that may interfere with the study

• Testosterone therapy beyond normal physiologic levels of the hormone within 3 months prior to study entry

• Initiation or change in physiologic testosterone replacement therapy within 3 months prior to study entry

• Hormonal anabolic therapies within 3 months prior to study entry

• Systemic cancer chemotherapy or immunomodulators (e.g., growth factors, immune globulin, interleukins, and interferons) within 60 days prior to study entry

• Lipid-lowering agents (except statins) within 30 days prior to study entry

• Any corticosteroid therapy above replacement levels within 30 days prior to study entry

• Untreated or uncontrolled hypertension

• Active AIDS-defining opportunistic infection (OI) within 30 days prior to study entry. People who have no evidence of active disease and are receiving maintenance therapy for AIDS-related OIs are not excluded.

• Acute illness that would interfere with the study within 30 days prior to study entry

• Investigational agents. People using expanded access investigational antiretroviral drugs are not excluded.

• Decreased mental capacity that may interfere with the study

• Pregnant or breastfeeding

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Ezetimibe

Locations

Country	Name	City	State
Puerto Rico	University of Puerto Rico	San Juan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	SUNY - Buffalo (Rochester)	Buffalo	New York
United States	Cook County Hospital Core Center	Chicago	Illinois
United States	Rush-Presbyterian/St. Lukes (Chicago)	Chicago	Illinois
United States	Feinberg School of Medicine, HIV/ACTU	Chicago, 60611-3015	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Dallas VA Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Texas, Galveston	Galveston	Texas
United States	University of Hawaii	Honolulu	Hawaii
United States	Indiana University Hospital	Indianapolis	Indiana
United States	Wishard Hospital	Indianapolis	Indiana
United States	UCLA School of Medicine	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Comprehensive Care Clinic	Nashville	Tennessee
United States	Beth Israel Medical Center	New York	New York
United States	Chelsea Clinic	New York	New York
United States	Columbia University	New York	New York
United States	NYU/Bellevue	New York	New York
United States	The Cornell Clinical Trials Unit	New York	New York
United States	Nebraska Health System	Omaha	Nebraska
United States	Presbyterian Medical Center - Univ. of PA	Philadelphia	Pennsylvania
United States	University of Pennsylvania, Philadelphia	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Stanley Street Treatment and Resource	Providence	Rhode Island
United States	The Miriam Hospital	Providence	Rhode Island
United States	Community Health Network, Inc.	Rochester	New York
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California, San Diego Antiviral Research Center	San Diego	California
United States	San Francisco General Hospital	San Francisco	California
United States	University of Washington (Seattle)	Seattle	Washington
United States	San Mateo County AIDS Program	Stanford	California
United States	Santa Clara Valley Medical Center	Stanford	California
United States	Stanford University	Stanford	California
United States	Willow Clinic	Stanford	California
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (4)

Calza L, Manfredi R, Chiodo F. Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother. 2004 Jan;53(1):10-4. Epub 2003 Nov 25. Review. — View Citation

Colagreco JP. Cardiovascular considerations in patients treated with HIV protease inhibitors. J Assoc Nurses AIDS Care. 2004 Jan-Feb;15(1):30-41. Review. — View Citation

Martínez E, Tuset M, Milinkovic A, Miró JM, Gatell JM. Management of dyslipidaemia in HIV-infected patients receiving antiretroviral therapy. Antivir Ther. 2004 Oct;9(5):649-63. Review. — View Citation

Visnegarwala F, Maldonado M, Sajja P, Minihan JL, Rodriguez-Barradas MC, Ong O, Lahart CJ, Hasan MQ, Balasubramanyam A, White AC Jr. Lipid lowering effects of statins and fibrates in the management of HIV dyslipidemias associated with antiretroviral therapy in HIV clinical practice. J Infect. 2004 Nov;49(4):283-90. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in directly measured fasting LDL-c while receiving ezetimibe compared to change while receiving placebo
Primary	changes in clinical symptoms and safety labs while receiving ezetimibe compared to changes in clinical symptoms while receiving placebo

External Links

•   Click here for more information about ACTG A5128
•   Click here for more information about hyperlipidemia
•   Haga clic aquí para más información acerca de la hiperlipidemia
•   Haga clic aquí para ver información sobre este ensayo clínico en español.