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

Condition(s) targeted: HIV Infections

Intervention: Ezetimibe (Drug)

Phase: N/A

Status: Active, not recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Susan Koletar, MD, Study Chair, Affiliation: Division of Infectious Diseases, Ohio State University
Dominic Chow, MD, MPH, Study Chair, Affiliation: University of Hawaii, Hawaii AIDS Clinical Research Program, Leahi Hospital

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.

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

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome:

Change in directly measured fasting LDL-c while receiving ezetimibe compared to change while receiving placebo

changes in clinical symptoms and safety labs while receiving ezetimibe compared to changes in clinical symptoms while receiving placebo

Detailed 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).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

University of Puerto Rico, San Juan 00936-5067, Puerto Rico

University of Alabama at Birmingham, Birmingham, Alabama 35924-2050, United States

Stanford University, Stanford, California 94305-5107, United States

San Mateo County AIDS Program, Stanford, California 94305-5107, United States

Willow Clinic, Stanford, California 94305-5107, United States

UCLA School of Medicine, Los Angeles, California 77555-0435, United States

San Francisco General Hospital, San Francisco, California 94110, United States

Santa Clara Valley Medical Center, Stanford, California 94305-5107, United States

University of California, San Diego Antiviral Research Center, San Diego, California 92103, United States

University of Southern California, Los Angeles, California 90033-1079, United States

Georgetown University Medical Center, Washington, District of Columbia 20007, United States

University of Miami, Miami, Florida 33136-1013, United States

University of Hawaii, Honolulu, Hawaii 96816-2396, United States

Rush-Presbyterian/St. Lukes (Chicago), Chicago, Illinois 60611-3015, United States

Cook County Hospital Core Center, Chicago, Illinois 60612, United States

Feinberg School of Medicine, HIV/ACTU, Chicago, 60611-3015, Illinois 60611-3015, United States

Indiana University Hospital, Indianapolis, Indiana 46202-5250, United States

Wishard Hospital, Indianapolis, Indiana 46202, United States

University of Minnesota, Minneapolis, Minnesota 55455-0392, United States

Nebraska Health System, Omaha, Nebraska 68198-5130, United States

The Cornell Clinical Trials Unit, New York, New York 10021, United States

SUNY - Buffalo (Rochester), Buffalo, New York 14215, United States

Beth Israel Medical Center, New York, New York 10003, United States

NYU/Bellevue, New York, New York 10016-6481, United States

University of Rochester Medical Center, Rochester, New York 14642-0001, United States

Community Health Network, Inc., Rochester, New York 14642-0001, United States

Chelsea Clinic, New York, New York 10011, United States

Columbia University, New York, New York 10032-3784, United States

Duke University Medical Center, Durham, North Carolina, United States

Ohio State University, Columbus, Ohio 43210, United States

University of Cincinnati, Cincinnati, Ohio 45267-0405, United States

MetroHealth Medical Center, Cleveland, Ohio 44109-1998, United States

University of Pennsylvania, Philadelphia, Philadelphia, Pennsylvania 19104, United States

Presbyterian Medical Center - Univ. of PA, Philadelphia, Pennsylvania 19104, United States

University of Pittsburgh, Pittsburgh, Pennsylvania 15213-2582, United States

The Miriam Hospital, Providence, Rhode Island 02906, United States

Rhode Island Hospital, Providence, Rhode Island 02906, United States

Stanley Street Treatment and Resource, Providence, Rhode Island 02906, United States

Comprehensive Care Clinic, Nashville, Tennessee 37203, United States

University of Texas, Galveston, Galveston, Texas 77555-0435, United States

Dallas VA Medical Center, Dallas, Texas 75235-9173, United States

University of Washington (Seattle), Seattle, Washington 98104, United States

Click here for more information about hyperlipidemia

Click here for more information about ACTG A5128

Haga clic aquí para ver información sobre este ensayo clínico en español.

Haga clic aquí para más información acerca de la hiperlipidemia

Related publications:

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.

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

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

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.

Last updated: December 7, 2007