A Randomized Study of Daily and Intermittent Prophylactic Regimens for the Prevention of Disseminated Mycobacterium Avium Complex (MAC) and Fungal Infections in HIV-Infected Patients

This study has been completed.

First Received: November 2, 1999 Last Updated: June 23, 2005 History of Changes

Sponsor:	Pfizer
Information provided by:	NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier:	NCT00002122

Purpose

PRIMARY: To determine the efficacy of azithromycin and rifabutin alone and in combination for the prevention of disseminated Mycobacterium avium Complex (MAC) infection in HIV-infected patients. To determine the efficacy of daily versus weekly fluconazole for the prevention of deep fungal infections in this patient population.

SECONDARY: To determine the incidence of bacterial (including mycobacterial) infections, cryptosporidiosis, and toxoplasmosis in azithromycin versus non-azithromycin containing regimens. To determine the incidence of oropharyngeal and vaginal candidiasis in patients treated with daily versus weekly fluconazole. To compare survival and outcomes of primary endpoints in the treatment arms.

Condition	Intervention	Phase
Mycoses Mycobacterium Avium-Intracellulare Infection HIV Infections	Drug: Azithromycin Drug: Rifabutin Drug: Fluconazole	Phase III

Study Type:	Interventional
Study Design:	Treatment, Double-Blind, Efficacy Study
Official Title:	A Randomized Study of Daily and Intermittent Prophylactic Regimens for the Prevention of Disseminated Mycobacterium Avium Complex (MAC) and Fungal Infections in HIV-Infected Patients

Resource links provided by NLM:

MedlinePlus related topics: AIDS Fungal Infections Molds

Drug Information available for: Rifabutin Azithromycin Fluconazole

U.S. FDA Resources

Further study details as provided by NIH AIDS Clinical Trials Information Service:

Estimated Enrollment:

720

Detailed Description:

Patients are randomized to receive azithromycin alone, rifabutin alone, or the two drugs in combination for MAC prophylaxis. Patients in each treatment group further receive one of two doses of concomitant fluconazole for deep fungal prophylaxis, unless specifically excluded for fluconazole randomization. Patients are followed for 1 to 2 years.

Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

Preventive therapy with isoniazid for M. tuberculosis.
Maintenance therapy for CMV retinitis.

Patients must have:

HIV infection or history of an AIDS-defining condition by CDC criteria.
One documented CD4 count < 100 cells/mm3 within 12 months prior to study entry.
NO active MAC disease, MAC bacteremia, or active mycobacterial infection (tuberculous or nontuberculous).
NO acute opportunistic infection.
Life expectancy of more than 6 months.
Consent of parent or guardian if less than legal age of consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

ALL PATIENTS -

Unexplained fevers, elevation in alkaline phosphatase, pancytopenia, abnormal liver function tests, or odynophagia for which the diagnoses of MAC and fungal infections have not been excluded.
Serious hypersensitivity reactions to macrolides or rifampin.
Unable to tolerate oral medications. FOR FLUCONAZOLE RANDOMIZATION -
Serious hypersensitivity reaction to fluconazole.
Active fungal infection (cryptococcosis, histoplasmosis, blastomycosis, aspergillosis, Candida esophagitis, thrush, vaginal candidiasis).
Positive baseline urine cryptococcal culture.

Concurrent Medication:

Excluded for fluconazole randomization:

Maintenance therapy for deep fungal infections.
Chronic therapy with ketoconazole or fluconazole.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002122

Locations

United States, California
UCSD Treatment Ctr / Dept of Medicine and Pediatrics
San Diego, California, United States, 92103
Santa Clara Valley Med Ctr
San Jose, California, United States, 951282699
Harbor - UCLA Med Ctr
Torrance, California, United States, 90509
UCI Med Ctr
Orange, California, United States, 92668
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
United States, District of Columbia
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
George Washington Univ Med Ctr
Washington, District of Columbia, United States, 20037
United States, Massachusetts
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, United States, 01655
United States, Pennsylvania
Univ of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77005
Univ of Texas Southwestern Med Ctr
Dallas, Texas, United States, 75235
Houston Veterans Administration Med Ctr
Houston, Texas, United States, 77030

Sponsors and Collaborators

Pfizer

More Information

Publications:

Havlir DV, Mccutchan JA, Bozzette SA, Dunne M. A double-blind, randomized study of weekly azithromycin, daily rifabutin, and combination azithromycin and rifabutin for the prevention of Mycobactetum avium complex (MAC) in AIDS patients. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:90

Study ID Numbers:	226A, 066-174
Study First Received:	November 2, 1999
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00002122 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:

Rifabutin
Mycobacterium avium-intracellulare Infection
Mycoses
Drug Therapy, Combination

Fluconazole
Acquired Immunodeficiency Syndrome
Azithromycin

Additional relevant MeSH terms:

Bacterial Infections
Communicable Diseases
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Rifabutin
Infection
Anti-Bacterial Agents
Mycoses
Gram-Positive Bacterial Infections
Therapeutic Uses
Azithromycin
Antifungal Agents
Retroviridae Infections
Fluconazole

RNA Virus Infections
Immune System Diseases
Acquired Immunodeficiency Syndrome
Pharmacologic Actions
Immunologic Deficiency Syndromes
Actinomycetales Infections
Mycobacterium Infections, Atypical
Antibiotics, Antitubercular
Mycobacterium avium-intracellulare Infection
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
Mycobacterium Infections
Antitubercular Agents

ClinicalTrials.gov processed this record on November 09, 2009