Trial Information

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)

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.