To compare the safety and effectiveness of fluconazole and amphotericin B as maintenance
treatment for preventing the relapse of cryptococcal meningitis in patients with AIDS.
Inclusion Criteria
Concurrent Medication:
Allowed:
- Antivirals such as zidovudine.
- Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia
(PCP).
- Pfizer must be notified if the patient is receiving ganciclovir (DHPG) at entry.
Concurrent Treatment:
Allowed:
- Radiation therapy for mucocutaneous Kaposi's sarcoma.
Patients must be oriented to person, place, and time, and able to give written informed
consent.
- Patients must have had an acute episode of cryptococcal meningitis that was documented
by recovery and identification of Cryptococcus neoformans from lumbar cerebrospinal
fluid (CSF) culture within 6 months prior to entry.
- Minimum total dose of 15 mg/kg of amphotericin B must have been given (either alone or
in combination with flucytosine) during primary therapy.
- Patients need not be receiving amphotericin B at the time of randomization but must
begin study maintenance therapy within 6 weeks of completion of primary amphotericin B
therapy. Patients may receive maintenance amphotericin B during the period between
completion of primary therapy and study entry.
Prior Medication:
Allowed:
- Antivirals such as zidovudine (AZT).
- Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia
(PCP).
Exclusion Criteria
Co-existing Condition:
Patients with the following are excluded:
- Clinical evidence of acute or chronic meningitis based upon any etiology other than
cryptococcosis.
- History of allergy or intolerance of imidazoles, azoles, or amphotericin B.
- Moderate or severe liver disease.
Concurrent Medication:
Excluded:
- Ketoconazole.
- Fluconazole.
- Itraconazole.
- Miconazole.
- Any systemic imidazole or azole for more than 7 days after initiation of primary
therapy for cryptococcosis.
- Intrathecal amphotericin B.
- Coumarin-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:
- Clinical evidence of acute or chronic meningitis based upon any etiology other than
cryptococcosis.
- History of allergy or intolerance of imidazoles, azoles, or amphotericin B.
- Moderate or severe liver disease.
- Inability to take oral medications reliably.
Prior Medication:
Excluded:
- Ketoconazole.
- Fluconazole.
- Itraconazole.
- Miconazole.
- Any systemic imidazole or azole for more than 7 days after initiation of primary
therapy for cryptococcosis.
- Intrathecal amphotericin B.
- Coumarin-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.
Prior Treatment:
Excluded:
- Lymphocyte replacement.
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Tucson Veterans Administration Med Ctr, Tucson, Arizona 85724, United States
Davies Med Ctr, San Francisco, California 94114, United States
Dr Richard Meyer, Los Angeles, California 90048, United States
Dr Paul Rothman, Sherman Oaks, California 91403, United States
Wilmington Hosp / Med Ctr of Delaware, Wilmington, Delaware 19899, United States
George Washington Univ Med Ctr, Washington, District of Columbia 20037, United States
Univ of Florida College of Medicine, Gainesville, Florida 32610, United States
Univ of South Florida, Tampa, Florida 33612, United States
DeKalb Gen Hosp, Decatur, Georgia 30033, United States
Med College of Georgia, Augusta, Georgia 30912, United States
Shallowford Hosp, Decatur, Georgia 30033, United States
Emory Univ School of Medicine, Atlanta, Georgia 30303, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Dr Michael Bach, Portland, Maine 04102, United States
Univ of Maryland / Inst of Human Virology, Baltimore, Maryland 212011192, United States
New England Med Ctr, Boston, Massachusetts 02111, United States
Univ Hosp, Boston, Massachusetts 02118, United States
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
Saint Michael's Med Ctr, Newark, New Jersey 07102, 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
Cabrini Med Ctr, New York, New York 10003, 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
Bowman Gray School of Medicine / North Carolina Baptist Hosp, Winston Salem, North Carolina 27103, United States
Cincinnati Veterans Adm Med Ctr / Univ Hosp, Cincinnati, Ohio 452670405, United States
Saint Michael's Hosp, Toronto, Ontario, Canada
Buckley Braffman Stern Med Associates, Philadelphia, Pennsylvania 19107, United States
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
Univ TX Galveston Med Branch, Galveston, Texas 77550, United States
Richmond AIDS Consortium, Richmond, Virginia 23219, United States
Dr Philip C Craven, Tacoma, Washington 98405, United States
CHG-118 Group Health / Cooperative of Puget Sound, Seattle, Washington 98112, United States
Powderly WG, Saag MS, Cloud GA, Robinson P, Meyer RD, Jacobson JM, Graybill JR, Sugar AM, McAuliffe VJ, Follansbee SE, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group. N Engl J Med. 1992 Mar 19;326(12):793-8.
Saag MS, Powderly WG, Cloud GA, Robinson P, Grieco MH, Sharkey PK, Thompson SE, Sugar AM, Tuazon CU, Fisher JF, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group. N Engl J Med. 1992 Jan 9;326(2):83-9.
