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

NCT00001030 | Completed Phase 3

• 3 other identifiers: ACTG 196CPCRA 00911172
• Study Type: interventional
• Target: 1,100
• Locations: 2 countries
• Sites: 42

Brief 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.

Conditions

Mycobacterium Avium-intracellulare Infection; HIV Infections

Keywords

Rifabutin; Mycobacterium avium-intracellulare Infection; Acquired Immunodeficiency Syndrome; Clarithromycin

Interventions

Clarithromycin DRUG

Rifabutin DRUG

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (42)

Alabama Therapeutics CRS

Birmingham, Alabama, 35294, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90095, United States

Location

Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.

Oakland, California, 94609, United States

Location

Ucsf Aids Crs

San Francisco, California, United States

Location

Howard University Hosp., Div. of Infectious Diseases, ACTU

Washington D.C., District of Columbia, 20059, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 33136, United States

Location

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, 96816, United States

Location

Chicago Children's CRS

Chicago, Illinois, 60611, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Cook County Hosp. CORE Ctr.

Chicago, Illinois, 60612, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60612, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202, United States

Location

Methodist Hosp. of Indiana

Indianapolis, Indiana, 46202, United States

Location

Univ. of Iowa Healthcare, Div. of Infectious Diseases

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, 02114, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, 02215, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

Hennepin County Med. Ctr., Div. of Infectious Diseases

Minneapolis, Minnesota, 55415, United States

Location

University of Minnesota, ACTU

Minneapolis, Minnesota, 55455, United States

Location

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

Omaha, Nebraska, 68198, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14215, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, 10021, United States

Location

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, 10029, United States

Location

Cornell University A2201

New York, New York, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, 10457, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas HealthCare System, Carolinas Med. Ctr.

Charlotte, North Carolina, 28203, United States

Location

Regional Center for Infectious Disease, Wendover Medical Center CRS

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 45267, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 43210, United States

Location

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, 19104, United States

Location

The Children's Hosp. of Philadelphia IMPAACT CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98122, United States

Location

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Mbeya, Tanzania

Location

Related Publications (9)

• 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)

  BACKGROUND

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

  PMID: 11364022 BACKGROUND

• 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)

  BACKGROUND

• 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. doi: 10.1097/00002030-200012220-00010.

  PMID: 11153670 BACKGROUND

• 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. doi: 10.2165/00003495-199700542-00004.

  PMID: 9358195 BACKGROUND

• 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. doi: 10.1097/00042560-199904150-00007.

  PMID: 10225227 BACKGROUND

• Fichtenbaum CJ, Powderly WG. Refractory mucosal candidiasis in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998 Mar;26(3):556-65. doi: 10.1086/514571.

  PMID: 9524822 BACKGROUND

• 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. doi: 10.1086/315380. Epub 2000 Apr 13.

  PMID: 10762562 BACKGROUND

• 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. doi: 10.1086/320515. Epub 2001 Apr 30.

  PMID: 11340534 BACKGROUND

MeSH Terms

Conditions

Mycobacterium avium-intracellulare Infection; HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Clarithromycin; Rifabutin

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Benson CA

  STUDY CHAIR

• Cohn DL

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: June 1, 1996
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

TA (1); US (41)