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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001030
• Other study ID #: ACTG 196
• Secondary ID: CPCRA 00911172
• Status: Completed
• Phase: Phase 3
• Est. completion date: June 1996

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1100
• Est. completion date: June 1996
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infections
• Mycobacterium avium-intracellulare Infection
• Mycobacterium Infections

Intervention

Drug:
• Clarithromycin

• Rifabutin

Locations

Country	Name	City	State
Tanzania	Mbeya Med. Research Program, Mbeya Referral Hosp. CRS	Mbeya
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Alabama Therapeutics CRS	Birmingham	Alabama
United States	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts
United States	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts
United States	Bmc Actg Crs	Boston	Massachusetts
United States	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts
United States	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Carolinas HealthCare System, Carolinas Med. Ctr.	Charlotte	North Carolina
United States	Chicago Children's CRS	Chicago	Illinois
United States	Cook County Hosp. CORE Ctr.	Chicago	Illinois
United States	Northwestern University CRS	Chicago	Illinois
United States	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	Case CRS	Cleveland	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	The Ohio State Univ. AIDS CRS	Columbus	Ohio
United States	Regional Center for Infectious Disease, Wendover Medical Center CRS	Greensboro	North Carolina
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana
United States	Methodist Hosp. of Indiana	Indianapolis	Indiana
United States	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa
United States	UCLA CARE Center CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	Hennepin County Med. Ctr., Div. of Infectious Diseases	Minneapolis	Minnesota
United States	University of Minnesota, ACTU	Minneapolis	Minnesota
United States	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York
United States	Cornell University A2201	New York	New York
United States	Memorial Sloan-Kettering Cancer Ctr.	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California
United States	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsf Aids Crs	San Francisco	California
United States	University of Washington AIDS CRS	Seattle	Washington
United States	Howard University Hosp., Div. of Infectious Diseases, ACTU	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Tanzania, 

References & Publications (9)

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. — View Citation

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. — View Citation

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)

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. — View Citation

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

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. — View Citation

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

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)

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. — View Citation