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: Flucytosine  Drug: Fluconazole  Drug: Amphotericin B

Ages Eligible for Study:  18 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.
• Any exceptions to these prohibitions of concomitant medications must be approved by Pfizer Central Research.

Concurrent Medication: Excluded:

• Coumadin-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.
• Excluded within 4 weeks of study entry:
• Greater than 1 mg/kg/wk amphotericin B.

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:

• Coumadin-type anticoagulants.
• Oral hypoglycemics.
• Barbiturates.
• Phenytoin.
• Immunostimulants.
• Investigational drugs or approved (licensed) drugs for investigational indications.
• Excluded within 4 weeks of study entry:
• Greater than 1 mg/kg/wk amphotericin B.

Prior Treatment: Excluded:

• Lymphocyte replacement.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
Arizona
      Tucson Veterans Administration Med Ctr, Tucson,  Arizona,  85724,  United States
California
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Dr Paul Rothman, Sherman Oaks,  California,  91403,  United States
      Dr Martin Mass, San Francisco,  California,  94120,  United States
      Dr Shelly Gordon, San Francisco,  California,  94115,  United States
Delaware
      Christiana Hosp / Med Ctr of Delaware, Wilmington,  Delaware,  19899,  United States
District of Columbia
      George Washington Univ Med Ctr, Washington,  District of Columbia,  20037,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
      Univ of South Florida, Tampa,  Florida,  33612,  United States
Georgia
      DeKalb Gen Hosp, Decatur,  Georgia,  30033,  United States
      Med College of Georgia, Augusta,  Georgia,  30912,  United States
      Emory Univ School of Medicine, Atlanta,  Georgia,  30303,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
Louisiana
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
      Louisiana State Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maine
      Dr Michael Bach, Portland,  Maine,  04102,  United States
Maryland
      Loch Raven Veterans Hosp, Baltimore,  Maryland,  21218,  United States
      Univ of Maryland / Inst of Human Virology, Baltimore,  Maryland,  212011192,  United States
Massachusetts
      New England Med Ctr, Boston,  Massachusetts,  02111,  United States
      Univ Hosp, Boston,  Massachusetts,  02118,  United States
Michigan
      Henry Ford Hosp, Detroit,  Michigan,  48202,  United States
      Harper Hosp, Detroit,  Michigan,  48201,  United States
      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
      Montefiore Med Ctr / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
      Bronx Veterans Administration / Mount Sinai Hosp, Bronx,  New York,  10468,  United States
      Columbia Univ, New York,  New York,  10032,  United States
      Jewish Hosp Ctr Affiliation, Jamaica,  New York,  11432,  United States
      Chelsea Village Med Ctr, New York,  New York,  10014,  United States
      Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York,  New York,  10037,  United States
      Albany Med College / AIDS Treatment Ctr, Albany,  New York,  12203,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States
North Carolina
      Univ of North Carolina School of Medicine, Chapel Hill,  North Carolina,  275997215,  United States
Ohio
      Cincinnati Veterans Adm Med Ctr / Univ Hosp, Cincinnati,  Ohio,  452670405,  United States
      Ohio State Univ Hosp, Columbus,  Ohio,  43210,  United States
Tennessee
      Univ of Tennessee, Memphis,  Tennessee,  38163,  United States
Texas
      United States Air Force Med Ctr, Lackland Air Force Base,  Texas,  782365300,  United States
      Dr Daniel Barbaro, Dallas,  Texas,  75235,  United States
      Univ TX San Antonio Health Science Ctr, San Antonio,  Texas,  78284,  United States
      Univ TX Galveston Med Branch, Galveston,  Texas,  77550,  United States
Virginia
      Richmond AIDS Consortium, Richmond,  Virginia,  23219,  United States
Washington
      CHG-118 Group Health / Cooperative of Puget Sound, Seattle,  Washington,  98112,  United States
Canada, Ontario
      Saint Michael's Hosp, Toronto,  Ontario,  Canada

Study ID Numbers:  012F; 056-159
Record last reviewed:  December 1989
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002305
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08