To evaluate the safety and effectiveness of fluconazole as treatment for acute cryptococcal meningitis in patients who have had an unsatisfactory response to or have experienced unacceptable toxicity with amphotericin B.

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

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.
• Aerosolized pentamidine.

Concurrent Treatment: Allowed:

• Radiation therapy for mucocutaneous Kaposi's sarcoma.

Not previously treated for acute cryptococcal meningitis and not eligible for Pfizer Central Research, protocol #159.

• Patients must have a baseline cerebrospinal fluid (CSF) culture-positive for Cryptococcus neoformans.
• Written informed consent must be obtained for each patient, either from the patient himself or from the patient's legal guardian.
• Each individual patient must be approved by Pfizer Central Research prior to study entry.

Prior Medication: Allowed:

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

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 or azoles.
• Moderate or severe liver disease.

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 or azoles.
• Moderate or severe liver disease.
• Satisfactory response to amphotericin B and have received a total amphotericin B dose of 15 mg/kg or more since CSF culture documentation of the current episode of acute cryptococcal meningitis.
• Life expectancy of < 2 weeks.

Prior Medication: Excluded:

• Coumadin-type anticoagulants.
• Oral hypoglycemics.
• Barbiturates.
• Phenytoin.
• Immunostimulants.
• Investigational drugs or approved (licensed) drugs for investigational indications.

Prior Treatment: Excluded:

• Lymphocyte replacement.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
District of Columbia
      George Washington Univ Med Ctr, Washington,  District of Columbia,  20037,  United States
Florida
      Univ of South Florida, Tampa,  Florida,  33612,  United States
Georgia
      Med College of Georgia, Augusta,  Georgia,  30912,  United States
      Emory Univ School of Medicine, Atlanta,  Georgia,  30303,  United States
Massachusetts
      Univ Hosp, Boston,  Massachusetts,  02118,  United States
Michigan
      Ann Arbor Veterans Administration Med Ctr, Ann Arbor,  Michigan,  48105,  United States
Missouri
      Washington Univ School of Medicine, St. Louis,  Missouri,  63108,  United States
New York
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      Bronx Veterans Administration / Mount Sinai Hosp, Bronx,  New York,  10468,  United States
Ohio
      Cincinnati Veterans Adm Med Ctr / Univ Hosp, Cincinnati,  Ohio,  452670405,  United States
Texas
      United States Air Force Med Ctr, Lackland Air Force Base,  Texas,  782365300,  United States
      Southwest Texas Methodist Hosp, San Antonio,  Texas,  78229,  United States
      Univ TX San Antonio Health Science Ctr, San Antonio,  Texas,  78284,  United States

Study ID Numbers:  012I; 056-161
Record last reviewed:  February 1990
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002306
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08