Clinical trial NCT00002122: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mycoses
Mycobacterium Avium-Intracellulare Infection
HIV Infections
Keywords: Rifabutin
Mycobacterium avium-intracellulare Infection
Mycoses
Drug Therapy, Combination
Fluconazole
Acquired Immunodeficiency Syndrome
Azithromycin
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 720
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Orange
country: United States
facility: UCI Med Ctr
state: California
city: San Diego
country: United States
facility: UCSD Treatment Ctr / Dept of Medicine and Pediatrics
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med Ctr
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Med Ctr
state: California
city: Washington
country: United States
facility: Georgetown Univ Med Ctr
state: District of Columbia
city: Washington
country: United States
facility: George Washington Univ Med Ctr
state: District of Columbia
city: Worcester
country: United States
facility: Univ of Massachusetts Med Ctr
state: Massachusetts
city: Philadelphia
country: United States
facility: Univ of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Univ of Texas Southwestern Med Ctr
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Veterans Administration Med Ctr
state: Texas
Study officials:
References:
citation: 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