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.

Condition	Treatment or Intervention	Phase
Mycobacterium avium-intracellulare Infection HIV Infections	Drug: Clarithromycin  Drug: Rifabutin	Phase III

Further Study Details: 

Expected Total Enrollment:  1100

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.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  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.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      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
Colorado
      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
Connecticut
      Yale Univ / New Haven, New Haven,  Connecticut,  065102483,  United States
Delaware
      Wilmington Hosp / Med Ctr of Delaware, Wilmington,  Delaware,  19899,  United States
District of Columbia
      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
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Georgia
      AIDS Research Consortium of Atlanta, Atlanta,  Georgia,  30308,  United States
Hawaii
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      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
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
Iowa
      Univ of Iowa Hosp and Clinic, Iowa City,  Iowa,  52242,  United States
Louisiana
      Louisiana Comm AIDS Rsch Prog / Tulane Univ Med, New Orleans,  Louisiana,  70112,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
      State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore,  Maryland,  212052196,  United States
Massachusetts
      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
Michigan
      Henry Ford Hosp, Detroit,  Michigan,  48202,  United States
Minnesota
      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
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
Nebraska
      Univ of Nebraska Med Ctr, Omaha,  Nebraska,  681985130,  United States
New Jersey
      North Jersey Community Research Initiative, Newark,  New Jersey,  071032842,  United States
New York
      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
North Carolina
      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
Ohio
      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
Oregon
      Portland Veterans Adm Med Ctr / Rsch & Education Grp, Portland,  Oregon,  972109951,  United States
Pennsylvania
      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
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ Texas Health Science Ctr / Univ Texas Med School, Houston,  Texas,  77030,  United States
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States
Virginia
      Richmond AIDS Consortium, Richmond,  Virginia,  23298,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States

Study chairs or principal investigators

Benson CA,  Study Chair
Cohn DL,  Study Chair

Study ID Numbers:  ACTG 196; CPCRA 009
Record last reviewed:  January 2003
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001030
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08