The Safety and Effectiveness of Clarithromycin and Rifabutin Used Alone or in Combination to Prevent Mycobacterium Avium Complex (MAC) or Disseminated MAC Disease in HIV-Infected Patients

Condition(s) targeted: Mycobacterium Avium-Intracellulare Infection; HIV Infections

Intervention: Clarithromycin (Drug); Rifabutin (Drug)

Phase: Phase 3

Status: Completed

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

Official(s) and/or principal investigator(s):
Benson CA, Study Chair
Cohn DL, Study Chair

To compare the efficacy and safety of clarithromycin alone versus rifabutin alone versus the two drugs in combination for the prevention or delay of Mycobacterium avium Complex (MAC) bacteremia or disseminated MAC disease. To compare other parameters such as survival, toxicity, and quality of life among the three treatment arms. To obtain information on the incidence and clinical grade of targeted gynecologic conditions.

Persons with advanced stages of HIV are considered to be at particular risk for developing disseminated MAC disease. The development of an effective regimen for the prevention of disseminated MAC disease may be of substantial benefit in altering the morbidity and possibly the mortality associated with this disease and its treatment.

Official title: A Prospective, Randomized, Comparative Study of the Safety and Efficacy of Clarithromycin Versus Rifabutin Versus the Combination of Clarithromycin Plus Rifabutin for the Prevention of Mycobacterium Avium Complex (MAC) Bacteremia or Disseminated MAC Disease in HIV-Infected Patients With CD4 Lymphocyte Counts <= 100 Cells/mm3

Study design: Treatment

Detailed description: Persons with advanced stages of HIV are considered to be at particular risk for developing disseminated MAC disease. The development of an effective regimen for the prevention of disseminated MAC disease may be of substantial benefit in altering the morbidity and possibly the mortality associated with this disease and its treatment.

Patients are randomized to receive clarithromycin alone, rifabutin alone, or the two drugs in combination daily. Patients are evaluated every 4 weeks for the first 8 weeks and every 8 weeks thereafter for the duration of the study. Patients are followed for 24 months. Per amendment, a pharmacokinetic substudy will be conducted.

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria

Concurrent Medication:

Recommended:

- PCP prophylaxis.

Allowed:

- GM-CSF or G-CSF.

- Erythropoietin.

- Therapies (including antiretrovirals) available through expanded access or treatment

IND programs.

- Other non-experimental therapies available by prescription.

- Antihistamines other than those specifically excluded.

Patients must have:

- Evidence or diagnosis of HIV infection or a history of an AIDS-defining condition by

CDC criteria.

- CD4 count <= 100 cells/mm3 within 90 days prior to study entry.

- Two baseline blood sample cultures negative for MAC within 30 days of study entry.

- No suspected disseminated MAC disease, in the opinion of the clinician.

NOTE:

- Patients with elevated GGT and/or triglycerides are allowed.

NOTE:

- Patients may co-enroll on ACTG 081/981/181, ACTG 175, ACTG 204, ACTG 193, ACTG 241, or

other acceptable protocols.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

- Known or suspected tuberculous infection or other non-tuberculous mycobacterial

infection requiring chemotherapy or chemoprophylaxis (with the exception of isoniazid prophylaxis alone).

NOTE:

- Patients may enroll who successfully completed tuberculosis (TB) treatment and have

been off anti-TB drugs for more than 6 months with no symptoms of mycobacterial infection.

- Active TB.

- Known hypersensitivity to study drugs.

- Malabsorption as defined by persistent diarrhea with more than 8 stools per day for >

6 weeks.

Concurrent Medication:

Excluded:

- Frequent (more than once per month), repeated, or continuous treatment courses of

quinolones, erythromycin, spiramycin, azithromycin, clarithromycin, or clindamycin.

- Concomitant terfenadine or astemizole.

Prior Medication:

Excluded:

- Prophylaxis with azithromycin, clarithromycin, or rifabutin for more than 4 months.

Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States

Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr, Sylmar, California 91342, United States

San Francisco Gen Hosp, San Francisco, California 941102859, United States

San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco, California 941102859, United States

Summitt Med Ctr / San Francisco Gen Hosp, Oakland, California 94609, United States

UCLA CARE Ctr, Los Angeles, California 90095, United States

Children's Hosp of Los Angeles, Los Angeles, California 90027, United States

Community Consortium of San Francisco, San Francisco, California 94110, United States

Highland Gen Hosp / San Francisco Gen Hosp, Oakland, California 946021018, United States

Olive View Med Ctr, Sylmar, California 91342, United States

Mountain States Reg Hemo Ctr / Univ of Colorado, Denver, Colorado 80262, United States

Denver CPCRA / Denver Public Hlth, Denver, Colorado 802044507, United States

Children's Hosp of Denver, Denver, Colorado 802181088, United States

Yale Univ / New Haven, New Haven, Connecticut 065102483, United States

Wilmington Hosp / Med Ctr of Delaware, Wilmington, Delaware 19899, United States

Veterans Administration Med Ctr / Regional AIDS Program, Washington, District of Columbia 20422, United States

Howard Univ, Washington, District of Columbia 20059, United States

Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States

Whitman - Walker Clinic / Georgetown Univ Med Ctr, Washington, District of Columbia 200072197, United States

HIV Ctr - District of Columbia Gen Hosp, Washington, District of Columbia 200072197, United States

Univ of Miami School of Medicine, Miami, Florida 331361013, United States

AIDS Research Consortium of Atlanta, Atlanta, Georgia 30308, United States

Univ of Hawaii, Honolulu, Hawaii 96816, United States

Children's Mem Hosp Family Cln / Northwestern Univ Med Schl, Chicago, Illinois 60611, United States

Lakeside Veterans Adm / Northwestern Univ Med School, Chicago, Illinois 60611, United States

Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States

Northwestern Univ Med School, Chicago, Illinois 60611, United States

Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States

AIDS Research Alliance - Chicago, Chicago, Illinois 60657, United States

Cook County Hosp, Chicago, Illinois 60612, United States

Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States

Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States

Univ of Iowa Hosp and Clinic, Iowa City, Iowa 52242, United States

Louisiana Comm AIDS Rsch Prog / Tulane Univ Med, New Orleans, Louisiana 70112, United States

Johns Hopkins Hosp, Baltimore, Maryland 21287, United States

State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore, Maryland 212052196, United States

Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States

Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States

Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States

Boston Med Ctr, Boston, Massachusetts 02118, United States

Henry Ford Hosp, Detroit, Michigan 48202, United States

Univ of Minnesota, Minneapolis, Minnesota 55455, United States

St Paul Ramsey Med Ctr, St. Paul, Minnesota 55101, United States

Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States

St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States

Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States

North Jersey Community Research Initiative, Newark, New Jersey 071032842, United States

Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Samaritan Village Inc / Bronx Municipal Hosp, Bronx, New York 10461, United States

SUNY / State Univ of New York, Syracuse, New York 13210, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

Mem Sloan - Kettering Cancer Ctr, New York, New York 10021, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States

Mount Sinai Med Ctr, New York, New York 10029, United States

Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States

Cornell Univ Med Ctr, New York, New York 10021, United States

Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States

Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States

SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States

Bronx Lebanon Hosp Ctr, Bronx, New York 10457, United States

Mount Sinai Med Ctr / Hemophilia Treatment Ctr, New York, New York 10029, United States

Clinical Directors Network of Region II, New York, New York 10011, United States

Beth Israel Med Ctr, New York, New York 10003, United States

City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States

Montefiore Med Ctr Adolescent AIDS Program, Bronx, New York 10467, United States

SUNY / Health Sciences Ctr at Brooklyn, Brooklyn, New York 112032098, United States

Saint Clare's Hosp and Health Ctr, New York, New York 10019, United States

North Shore Univ Hosp, Manhasset, New York 11030, United States

North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States

Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Columbia Presbyterian Med Ctr, New York, New York 100323784, United States

Adirondack Med Ctr at Saranac Lake, Albany, New York 122083479, United States

Mid - Hudson Care Ctr, Albany, New York 122083479, United States

Albany Med College / Division of HIV Medicine A158, Albany, New York 122083479, United States

Carolinas Med Ctr, Charlotte, North Carolina 28203, United States

Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States

Moses H Cone Memorial Hosp, Greensboro, North Carolina 27401, United States

Glaxo Wellcome Inc, Research Triangle Park, North Carolina 27709, United States

Case Western Reserve Univ, Cleveland, Ohio 44106, United States

Univ of Cincinnati, Cincinnati, Ohio 452670405, United States

Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States

Med College of Ohio, Toledo, Ohio 43699, United States

MetroHealth Med Ctr, Cleveland, Ohio 441091998, United States

Portland Veterans Adm Med Ctr / Rsch & Education Grp, Portland, Oregon 972109951, United States

Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States

Children's Hosp of Philadelphia, Philadelphia, Pennsylvania 191044318, United States

Thomas Jefferson Univ Hosp, Philadelphia, Pennsylvania 191075098, United States

Julio Arroyo, West Columbia, South Carolina 29169, United States

Univ Texas Health Science Ctr / Univ Texas Med School, Houston, Texas 77030, United States

Univ of Texas Galveston, Galveston, Texas 775550435, United States

Richmond AIDS Consortium, Richmond, Virginia 23298, United States

Univ of Washington, Seattle, Washington 981224304, United States

Click here for more information about Rifabutin

Click here for more information about Clarithromycin

Related publications:

Currier JS, Williams P, Feinberg J, Becker S, Owens S, Benson CA. ACTG 815: a prospective study of bacterial infections in advanced HIV disease. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:131 (abstract no 364)

Mascolini M. FDA advisory committee deadlocks on delavirdine. Food and Drug Administration. AIDS Treat News. 1996 Dec 6;(No 260):3-5. No abstract available.

Watts DH, Spino C, Benson C, Yu B, Katzenstein D, Hammer S, Stratton P, Korvick J. A comparison of gynecologic findings in HIV-positive women with CD4 lymphocyte counts 200 to 500/cc and less than 100/cc. Int Conf AIDS. 1996 Jul 7-12;11(2):275 (abstract no ThB4137)

Fichtenbaum CJ, Zackin R, Feinberg J, Benson C, Griffiths JK. Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection. AIDS. 2000 Dec 22;14(18):2889-93.

Cohn DL. Prevention strategies for Mycobacterium avium-intracellulare complex (MAC) infection. A review of recent studies in patients with AIDS. Drugs. 1997;54 Suppl 2:8-15; discussion 28-9. Review.

Watts DH, Spino C, Zaborski L, Katzenstein D, Hammer S, Benson C. Comparison of gynecologic history and laboratory results in HIV-positive women with CD4+ lymphocyte counts between 200 and 500 cells/microl and below 100 cells/microl. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Apr 15;20(5):455-62.

Fichtenbaum CJ, Powderly WG. Refractory mucosal candidiasis in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998 Mar;26(3):556-65. Review.

Benson CA, Williams PL, Cohn DL, Becker S, Hojczyk P, Nevin T, Korvick JA, Heifets L, Child CC, Lederman MM, Reichman RC, Powderly WG, Notario GF, Wynne BA, Hafner R. Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial. The AIDS Clinical Trials Group 196/Terry Beirn Community Programs for Clinical Research on AIDS 009 Protocol Team. J Infect Dis. 2000 Apr;181(4):1289-97.

Currier JS, Williams P, Feinberg J, Becker S, Owens S, Fichtenbaum C, Benson C. Impact of prophylaxis for Mycobacterium avium complex on bacterial infections in patients with advanced human immunodeficiency virus disease. Clin Infect Dis. 2001 Jun 1;32(11):1615-22.

Last updated: June 23, 2005