Randomized Comparative Study of Fluconazole Versus Clotrimazole Troches in the Prevention of Serious Fungal Infection in Patients With AIDS or Advanced AIDS-Related Complex. (A Nested Study of ACTG 081)

Phase 3

Completed

• Conditions: Candidiasis; Mycoses; HIV Infections

• Registration Number: NCT00000676
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

To study the effectiveness, safety, and tolerance of fluconazole versus clotrimazole troches (lozenges) as prophylaxis (preventive treatment) against fungal infections in patients enrolled in ACTG 081 (a study of prophylaxis against pneumocystosis, toxoplasmosis, and serious bacterial infection). Primarily, to compare the rates of invasive infections by C. neoformans, endemic mycoses, and Candida. To compare the mortality rates due to fungal infections between two antifungal prophylactic treatments. Secondarily, to assess the effect of prophylaxis on the incidence of severe fungal infections, defined as invasive infections and esophageal candidiasis and less severe mucocutaneous infection.

Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.

Detailed Description

Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.

AMENDED: 11/01/90 Sufficient numbers of patients will be enrolled from all centers starting at week 8 of participation in the parent study to achieve a total of 240 evaluable patients who will remain in the nested study for a maximum duration of 45 months. Enrollment will continue until all eligible and interested 081 patients are enrolled. Fungal prophylaxis will begin at the time of enrollment into the nested study and will continue until an efficacy or safety end point is reached, until withdrawal from the nested study, or until death.

Original design: Patients included are those already enrolled in ACTG 081. Patients are enrolled from all centers at either week 8, 12, 16, 20, 24, 28, or 32 of participation in the parent study. They are randomized to receive either oral fluconazole or clotrimazole troches. Prophylaxis continues until a serious fungal infection develops, the end of the parent study is reached (which is expected to be December 1991), the patient withdraws from either the nested or parent study, or the patient dies. Clinical examination is performed at 2 weeks and then monthly (or more if clinically indicated) for the duration of antifungal prophylaxis; the schedule of evaluation is the same as for the parent study. There is a 1-month postprophylaxis follow-up after discontinuation of prophylaxis for any reason.

Study Timeline

• Study Completion: 1993-11
• Study First Submitted: 1999-11-02
• Study First Submitted QC: 2001-08-30
• Study First Posted: 2001-08-31
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-26
• Last Update Posted: 2021-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Trial Locations

Locations (26)

Stanford CRS; 🇺🇸 Palo Alto, California, United States

Ucsd, Avrc Crs; 🇺🇸 San Diego, California, United States

Ucsf Aids Crs; 🇺🇸 San Francisco, California, United States

Univ. of Miami AIDS CRS; 🇺🇸 Miami, Florida, United States

Northwestern University CRS; 🇺🇸 Chicago, Illinois, United States

Rush Univ. Med. Ctr. ACTG CRS; 🇺🇸 Chicago, Illinois, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic; 🇺🇸 Indianapolis, Indiana, United States

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU; 🇺🇸 New Orleans, Louisiana, United States

Johns Hopkins Adult AIDS CRS; 🇺🇸 Baltimore, Maryland, United States

Bmc Actg Crs; 🇺🇸 Boston, Massachusetts, United States

Scroll for more (16 remaining)