To compare the safety and effectiveness of a new drug, fluconazole, with that of the usual therapy, amphotericin B, in the prevention of a relapse of cryptococcal meningitis (CM) in patients with AIDS who have been successfully treated for acute CM in the last 6 months. Cryptococcal meningitis is a life-threatening infectious complication of AIDS. Because relapse after treatment occurs in over 50 percent of cases, chronic maintenance therapy with intravenous (IV) amphotericin B is usually given. However, amphotericin B is not always effective, has toxic effects, and must be given by the intravenous route. Fluconazole is an antifungal agent that can be given orally and has been shown to be effective against cryptococcal infections in animals and against acute CM in a few AIDS patients. Also, the side effects experienced by over 2000 patients or volunteers given fluconazole have seldom been severe enough to require withdrawal of the drug.

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

Further Study Details: 

Expected Total Enrollment:  330

Cryptococcal meningitis is a life-threatening infectious complication of AIDS. Because relapse after treatment occurs in over 50 percent of cases, chronic maintenance therapy with intravenous (IV) amphotericin B is usually given. However, amphotericin B is not always effective, has toxic effects, and must be given by the intravenous route. Fluconazole is an antifungal agent that can be given orally and has been shown to be effective against cryptococcal infections in animals and against acute CM in a few AIDS patients. Also, the side effects experienced by over 2000 patients or volunteers given fluconazole have seldom been severe enough to require withdrawal of the drug.

Patients accepted in the trial are randomly assigned to fluconazole or amphotericin B. Fluconazole is given orally once a day and amphotericin B is given intravenously once a week. Dosages depend on body weight. Medications may be given with amphotericin B to prevent or reduce discomfort from associated side effects. Patients are treated for 12 months and may continue to receive antiviral therapy, radiation therapy for mucocutaneous Kaposi's sarcoma, or preventive therapy for Pneumocystis carinii pneumonia (PCP) during the study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• HIV infection documented by antibody (ELISA on two occasions or ELISA with Western blot confirmation), p24 antigen testing, or recovery of HIV in culture.

Prior Medication: Required:

• Minimum total dose of 15 mg/kg of amphotericin B (either alone or in combination with flucytosine) during primary therapy. End of primary therapy within 6 weeks of start of maintenance therapy.
• Allowed:
• Past or present antiviral therapy and prophylaxis for Pneumocystis carinii pneumonia (PCP).
• Pfizer must be notified if the patient is receiving ganciclovir at entry. Allowed with amphotericin B to treat or prevent side effects.
• Antipyretics.
• Hydrocortisone.
• Meperidine.

Exclusion Criteria

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

• Clinical evidence of acute or chronic meningitis other than cryptococcosis.
• Allergy or intolerance of imidazoles, azoles, or amphotericin B. Unable to take oral medications reliably.

Patients with the following are excluded:

• Clinical evidence of acute or chronic meningitis other than cryptococcosis.
• Allergy or intolerance of imidazoles, azoles, or amphotericin B.

Prior Medication: Excluded for more than 7 days after initiation of primary therapy for cryptococcosis:

• Ketoconazole.
• Fluconazole.
• Itraconazole.
• Miconazole.
• Any other systemic imidazole or azole.
• Excluded:
• Intrathecal amphotericin B.
• Coumadin-type anticoagulants.
• Oral hypoglycemics.
• Barbiturates.
• Phenytoin.
• Immunostimulants.
• Investigational drug or approved (licensed) drugs for investigational indications.

Prior Treatment: Excluded:

• Lymphocyte replacement.

California
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  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
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
New York
      SUNY - Stony Brook, Stony Brook,  New York,  117948153,  United States
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Jack Weiler Hosp / Bronx Municipal Hosp, Bronx,  New York,  10465,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  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
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      Beth Israel Med Ctr / Peter Krueger Clinic, New York,  New York,  10003,  United States
      City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst,  New York,  11373,  United States
      North Central Bronx Hosp / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
Ohio
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
      Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati,  Ohio,  452670405,  United States
      Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States

Study chairs or principal investigators

Armstrong D,  Study Chair
Dismukes W,  Study Chair
Powderly W,  Study Chair

Study ID Numbers:  ACTG 026; 056-158; FDA 12E
Record last reviewed:  September 2002
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001017
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08