To compare the safety and effectiveness of fluconazole and amphotericin B, alone or in combination with flucytosine, as treatment for acute cryptococcal meningitis.

Condition	Treatment or Intervention
Meningitis, Cryptococcal HIV Infections	Drug: Fluconazole  Drug: Amphotericin B

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Allowed:

• Immunosuppressant therapy.
• Antiviral therapy such as zidovudine.
• Prophylaxis for Pneumocystis carinii pneumonia.

Concurrent Treatment: Allowed:

• Radiation therapy for mucocutaneous Kaposi's sarcoma.

Written informed consent must be obtained for each patient, either from the patient himself or from the patient's legal guardian.

• No prior systemic antifungal therapy for cryptococcosis.
• Relapse after prior therapy.
• Success of prior therapy must have been documented by negative cerebrospinal fluid (CSF) culture at the end of therapy. Following prior therapy, such patients may not have received more than 1 mg/kg/wk amphotericin B in the 4 weeks before entry into study.

Prior Medication: Allowed:

• Immunosuppressant therapy.
• Antiviral therapy such as zidovudine.
• Prophylaxis for Pneumocystis carinii pneumonia.

Exclusion Criteria

Co-existing Condition: Patients with the following are excluded:

• Evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis.
• History of allergy to or intolerance of imidazoles, azoles, or amphotericin B.
• Moderate or severe liver disease.
• Comatose.
• Unlikely to survive more than 2 weeks.

Concurrent Medication: Excluded within 4 weeks of study entry:

• Greater than 1 mg/kg/wk amphotericin B.
• Coumadin-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:

• Evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis.
• History of allergy to or intolerance of imidazoles, azoles, or amphotericin B.
• Moderate or severe liver disease.
• Comatose.
• Unlikely to survive more than 2 weeks.

Prior Medication: Excluded within 4 weeks of study entry:

• Greater than 1 mg/kg/wk amphotericin B.
• Coumadin-type anticoagulants.
• Oral hypoglycemics.
• Barbiturates.
• Phenytoin.
• Immunostimulants.
• Investigational drugs or approved (licensed) drugs for investigational indications.

Prior Treatment: Excluded:

• Lymphocyte replacement.

California
      Davies Med Ctr, San Francisco,  California,  94114,  United States
Delaware
      Christiana Hosp / Med Ctr of Delaware, Wilmington,  Delaware,  19899,  United States
Florida
      Univ of South Florida, Tampa,  Florida,  33612,  United States
Maryland
      Univ of Maryland / Inst of Human Virology, Baltimore,  Maryland,  212011192,  United States
Michigan
      Henry Ford Hosp, Detroit,  Michigan,  48202,  United States
New York
      Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York,  New York,  10037,  United States
Tennessee
      Univ of Tennessee, Memphis,  Tennessee,  38163,  United States
Canada, Ontario
      Saint Michael's Hosp, Toronto,  Ontario,  Canada

Study ID Numbers:  012H; 056-159B
Record last reviewed:  February 1990
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002068
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08