a study of fluconazole in the treatment of cryptococcal meningitis in patients with aids

Conditions: Meningitis, Cryptococcal; HIV Infections

Summary: to compare the safety and effectiveness of fluconazole with that of placebo as maintenance treatment for preventing the relapse of cryptococcal meningitis in patients with aids.


Eligibility criteria:
inclusion criteria concurrent medication: allowed: * antiviral therapy (e.g., zidovudine). * prophylaxis (including aerosolized pentamidine) for pneumocystis carinii pneumonia (pcp). concurrent treatment: allowed: * radiation therapy for mucocutaneous kaposi's sarcoma. patients must be oriented to person, place, and time and able to give written informed consent. * patients must have had an acute episode of cryptococcal meningitis that was documented by recovery and identification of cryptococcus from lumbar cerebrospinal fluid (csf) culture within 4 months of study entry. * adequate therapy will consist of 6 - 16 weeks of treatment with amphotericin b alone, amphotericin b + oral flucytosine, or a period of the combination followed by amphotericin alone. adequate regimens will include: * a minimum total amphotericin b dose of 2 grams as monotherapy. * 6 weeks of flucytosine at 150 mg/kg/day (or levels of 20 to 100 mcg/ml demonstrated) plus amphotericin b at an average daily dose of at least 0.3 mg/kg/day or to a total dose of 1 gram. * after a shorter period of the combination amphotericin/flucytosine therapy, an additional y grams of amphotericin b monotherapy will make therapy adequate where y = 2 gm-(x weeks combination therapy / 3 weeks). * for example, a patient who received 3 weeks of combination followed by amphotericin alone would need an additional 2 gm - 3 weeks/3 weeks = 1 gm of amphotericin b. * patients need not be receiving amphotericin b at the time of randomization but must begin study maintenance therapy within 3 weeks of cessation of primary amphotericin b therapy. prior medication: allowed: * antiviral therapy (e.g., zidovudine (azt)). * prophylaxis (including aerosolized pentamidine) for pneumocystis carinii pneumonia (pcp). exclusion criteria co-existing condition: patients with the following are excluded: * clinical evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis. * history of allergy or intolerance of imidazoles, azoles, or amphotericin b. * moderate or severe liver disease. concurrent medication: excluded: * intrathecal amphotericin b. * coumarin-type anticoagulants. * oral hypoglycemics. * barbiturates. * phenytoin. * immunostimulants. * investigational drugs or approved (licensed) drugs for investigational indications. concurrent treatment: excluded: * lymphocyte replacement. patients with the following are excluded: * clinical evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis. * history of allergy or intolerance of imidazoles, azoles, or amphotericin b. * moderate or severe liver disease defined by specific lab values. * inability to take oral medications reliably. prior medication: excluded: * intrathecal amphotericin b. * coumarin-type anticoagulants. * oral hypoglycemics. * barbiturates. * phenytoin. * immunostimulants. * investigational drugs or approved (licensed) drugs for investigational indications. prior treatment: excluded: * lymphocyte replacement.

Keywords: aids-related opportunistic infections meningitis cryptococcosis fluconazole acquired immunodeficiency syndrome