Multicenter Comparison of Fluconazole (UK-49,858) and Amphotericin B as Maintenance Treatment for the Prevention of Relapse of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome

To compare the safety and effectiveness of fluconazole and amphotericin B as maintenance treatment for preventing the relapse of cryptococcal meningitis in patients with AIDS.


Eligibility Criteria:
Inclusion Criteria

Concurrent Medication:

Allowed:

* Antivirals such as zidovudine.
* Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia (PCP).
* Pfizer must be notified if the patient is receiving ganciclovir (DHPG) at entry.

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 neoformans from lumbar cerebrospinal fluid (CSF) culture within 6 months prior to entry.
* Minimum total dose of 15 mg/kg of amphotericin B must have been given (either alone or in combination with flucytosine) during primary therapy.
* Patients need not be receiving amphotericin B at the time of randomization but must begin study maintenance therapy within 6 weeks of completion of primary amphotericin B therapy. Patients may receive maintenance amphotericin B during the period between completion of primary therapy and study entry.

Prior Medication:

Allowed:

* Antivirals such as 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:

* Ketoconazole.
* Fluconazole.
* Itraconazole.
* Miconazole.
* Any systemic imidazole or azole for more than 7 days after initiation of primary therapy for cryptococcosis.
* 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.
* Inability to take oral medications reliably.

Prior Medication:

Excluded:

* Ketoconazole.
* Fluconazole.
* Itraconazole.
* Miconazole.
* Any systemic imidazole or azole for more than 7 days after initiation of primary therapy for cryptococcosis.
* Intrathecal amphotericin B.
* Coumarin-type anticoagulants.
* Oral hypoglycemics.
* Barbiturates.
* Phenytoin.
* Immunostimulants.
* Investigational drugs or approved (licensed) drugs for investigational indications.
* Any exceptions to these prohibitions of concomitant medications must be approved by Pfizer Central Research.

Prior Treatment:

Excluded:

* Lymphocyte replacement.