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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00002122

Collaborator

(none)

720

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Mycoses Mycobacterium Avium-Intracellulare Infection HIV Infections	Drug: Azithromycin Drug: Rifabutin Drug: Fluconazole	Phase 3

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.

Study Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Treatment

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 0 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles County - USC Med Ctr	Los Angeles	California	United States	90033
2	UCI Med Ctr	Orange	California	United States	92668
3	UCSD Treatment Ctr / Dept of Medicine and Pediatrics	San Diego	California	United States	92103
4	Santa Clara Valley Med Ctr	San Jose	California	United States	951282699
5	Harbor - UCLA Med Ctr	Torrance	California	United States	90509
6	Georgetown Univ Med Ctr	Washington	District of Columbia	United States	20007
7	George Washington Univ Med Ctr	Washington	District of Columbia	United States	20037
8	Univ of Massachusetts Med Ctr	Worcester	Massachusetts	United States	01655
9	Univ of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
10	Univ of Texas Southwestern Med Ctr	Dallas	Texas	United States	75235
11	Baylor College of Medicine	Houston	Texas	United States	77005
12	Houston Veterans Administration Med Ctr	Houston	Texas	United States	77030