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
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
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
Summary
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.
Clinical Details
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: Primary Purpose: 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.
Eligibility
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.
Locations and Contacts
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS, Mbeya, Tanzania
Alabama Therapeutics CRS, Birmingham, Alabama 35294, United States
UCLA CARE Center CRS, Los Angeles, California 90095, United States
Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab., Oakland, California 94609, United States
Ucsf Aids Crs, San Francisco, California, United States
Howard University Hosp., Div. of Infectious Diseases, ACTU, Washington, District of Columbia 20059, United States
Univ. of Miami AIDS CRS, Miami, Florida 33136, United States
Univ. of Hawaii at Manoa, Leahi Hosp., Honolulu, Hawaii 96816, United States
Chicago Children's CRS, Chicago, Illinois 60611, United States
Cook County Hosp. CORE Ctr., Chicago, Illinois 60612, United States
Northwestern University CRS, Chicago, Illinois 60611, United States
Rush Univ. Med. Ctr. ACTG CRS, Chicago, Illinois 60612, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic, Indianapolis, Indiana 46202, United States
Methodist Hosp. of Indiana, Indianapolis, Indiana 46202, United States
Univ. of Iowa Healthcare, Div. of Infectious Diseases, Iowa City, Iowa 52242, United States
Johns Hopkins Adult AIDS CRS, Baltimore, Maryland 21287, United States
Beth Israel Deaconess - East Campus A0102 CRS, Boston, Massachusetts 02215, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS, Boston, Massachusetts 02215, United States
Bmc Actg Crs, Boston, Massachusetts 02118, United States
Massachusetts General Hospital ACTG CRS, Boston, Massachusetts 02114, United States
Hennepin County Med. Ctr., Div. of Infectious Diseases, Minneapolis, Minnesota 55415, United States
University of Minnesota, ACTU, Minneapolis, Minnesota 55455, United States
St. Louis ConnectCare, Infectious Diseases Clinic, St Louis, Missouri, United States
Washington U CRS, St. Louis, Missouri, United States
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr., Omaha, Nebraska 68198, United States
Bronx-Lebanon Hosp. IMPAACT CRS, Bronx, New York 10457, United States
SUNY - Buffalo, Erie County Medical Ctr., Buffalo, New York 14215, United States
Beth Israel Med. Ctr. (Mt. Sinai), New York, New York 10029, United States
Cornell University A2201, New York, New York, United States
Memorial Sloan-Kettering Cancer Ctr., New York, New York 10021, United States
NY Univ. HIV/AIDS CRS, New York, New York 10016, United States
Univ. of Rochester ACTG CRS, Rochester, New York 14642, United States
Unc Aids Crs, Chapel Hill, North Carolina 27599, United States
Carolinas HealthCare System, Carolinas Med. Ctr., Charlotte, North Carolina 28203, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS, Greensboro, North Carolina 27401, United States
Univ. of Cincinnati CRS, Cincinnati, Ohio 45267, United States
Case CRS, Cleveland, Ohio 44106, United States
MetroHealth CRS, Cleveland, Ohio 44109, United States
The Ohio State Univ. AIDS CRS, Columbus, Ohio 43210, United States
Hosp. of the Univ. of Pennsylvania CRS, Philadelphia, Pennsylvania 19104, United States
The Children's Hosp. of Philadelphia IMPAACT CRS, Philadelphia, Pennsylvania 19104, United States
University of Washington AIDS CRS, Seattle, Washington 98122, United States
Additional Information
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. 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; AIDS Clinical Trials Group New Works Concept Sheet Team 064. 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. Epub 2000 Apr 13. Currier JS, Williams P, Feinberg J, Becker S, Owens S, Fichtenbaum C, Benson C; Adult Clinical Trial Group. 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. Epub 2001 Apr 30.
Last updated: June 2, 2015
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