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.
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.
Dr Paul Rothman, Sherman Oaks, California 91403, United States
UCSD, San Diego, California 92103, United States
Dr Robert Larsen, Los Angeles, California 90033, United States
UCI Med Ctr, Orange, California 92668, United States
Stanford Univ School of Medicine, Stanford, California 94305, United States
