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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002122
• Other study ID #: 226A
• Secondary ID: 066-174
• Status: Completed
• Phase: Phase 3
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: April 1996
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 720
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infection
• Mycobacterium Avium-Intracellulare Infection
• Mycobacterium Infections
• Mycoses

Intervention

Drug:
• Azithromycin

• Rifabutin

• Fluconazole

Locations

Country	Name	City	State
United States	Univ of Texas Southwestern Med Ctr	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Houston Veterans Administration Med Ctr	Houston	Texas
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCI Med Ctr	Orange	California
United States	Univ of Pennsylvania	Philadelphia	Pennsylvania
United States	UCSD Treatment Ctr / Dept of Medicine and Pediatrics	San Diego	California
United States	Santa Clara Valley Med Ctr	San Jose	California
United States	Harbor - UCLA Med Ctr	Torrance	California
United States	George Washington Univ Med Ctr	Washington	District of Columbia
United States	Georgetown Univ Med Ctr	Washington	District of Columbia
United States	Univ of Massachusetts Med Ctr	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (1)

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