To evaluate the effect of corticosteroids on reducing elevated intracranial pressure in cryptococcal meningitis. To evaluate the safety of corticosteroids in patients with cryptococcal meningitis and intracranial hypertension. In AIDS patients with cryptococcal meningitis, a correlation has been found between early death and elevated intracranial pressure. Since dexamethasone has been found to reduce intracranial pressure resulting from other forms of meningitis, it may be of benefit in AIDS patients with cryptococcal meningitis.

Condition	Treatment or Intervention	Phase
Meningitis, Cryptococcal HIV Infections	Drug: Flucytosine  Drug: Fluconazole  Drug: Amphotericin B  Drug: Dexamethasone	Phase II

Further Study Details: 

Expected Total Enrollment:  36

In AIDS patients with cryptococcal meningitis, a correlation has been found between early death and elevated intracranial pressure. Since dexamethasone has been found to reduce intracranial pressure resulting from other forms of meningitis, it may be of benefit in AIDS patients with cryptococcal meningitis.

Patients are randomized to receive dexamethasone or placebo every 6 hours for 72 hours (days 1 through 3). Additionally, standard antifungal therapy with amphotericin B and flucytosine is given for 2 weeks, followed by fluconazole for 8 weeks. Lumbar punctures will be performed daily on days 1 through 3, on days 7 and 14, and at week 10.

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

Criteria

Inclusion Criteria

Concurrent Medication: Allowed:

• Aerosolized pentamidine or systemic chemoprophylaxis for PCP.
• Preventive therapy for steroid-associated ulcers and any other therapies required to manage steroid toxicity (e.g., insulin).

Patients must have:

• Documented initial episode or relapse of acute cryptococcal meningitis. (NOTE: Patients must be untreated for this episode except for administration of a test dose of 1 g or less amphotericin B.)
• Acute cryptococcal meningitis with cerebrospinal fluid opening pressure >= 250 mm H2O prior to receipt of antifungal therapy for this episode.
• Documented HIV infection OR a diagnosis of AIDS based on a documented AIDS-defining opportunistic infection.
• Ability to begin therapy within 8 hours after the pre-entry lumbar puncture.
• Consent of parent or guardian if less than 18 years of age.

NOTE:

• Comatose patients eligible provided informed consent can be provided by guardian or next of kin.

Exclusion Criteria

Co-existing Condition: Patients with the following symptoms or conditions are excluded:

• Concurrent CNS disease such as another infection or neoplasm that would interfere with assessment of response.
• Prison incarceration.

Concurrent Medication: Excluded:

• Acetazolamide, mannitol, urea preparations, and other corticosteroids during the first 72 hours of the study.
• Treatment or prophylaxis with other systemic antifungal agents at any time.
• Antiretroviral therapy during the first 72 hours of the study.

Prior Medication: Excluded within 7 days prior to study entry:

• Corticosteroids, mannitol, urea preparations, acetazolamide, or more than 24 hours of phenytoin.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
District of Columbia
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
New York
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Jack Weiler Hosp / Bronx Municipal Hosp, Bronx,  New York,  10465,  United States
      Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx,  New York,  10461,  United States
      Bronx Veterans Administration / Mount Sinai Hosp, Bronx,  New York,  10468,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      SUNY / Health Sciences Ctr at Brooklyn, Brooklyn,  New York,  112032098,  United States
Ohio
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

J Jacobson,  Study Chair

Study ID Numbers:  ACTG 202
Record last reviewed:  October 1996
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000776
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08