Comparison of Fluconazole and Amphotericin B in the Treatment of Brain Infections in Patients With AIDS

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001017
First received: November 2, 1999
Last updated: March 11, 2011
Last verified: September 2002
  Purpose

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 Intervention Phase
Meningitis, Cryptococcal
HIV Infections
Drug: Fluconazole
Drug: Amphotericin B
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Comparison of Fluconazole (UK-49,858) and Amphotericin B for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 330
Primary Completion Date: July 1991 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001017

Locations
United States, California
UCLA CARE Ctr
Los Angeles, California, United States, 90095
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Louisiana
Louisiana State Univ School of Medicine
New Orleans, Louisiana, United States, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
United States, New York
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, United States, 10003
Mount Sinai Med Ctr
New York, New York, United States, 10029
Cornell Univ Med Ctr
New York, New York, United States, 10021
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY - Stony Brook
Stony Brook, New York, United States, 117948153
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Ohio
Holmes Hosp / Univ of Cincinnati Med Ctr
Cincinnati, Ohio, United States, 452670405
Univ Hosp of Cleveland / Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
Sponsors and Collaborators
Pfizer
Investigators
Study Chair: Armstrong D
Study Chair: Dismukes W
Study Chair: Powderly W
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001017     History of Changes
Other Study ID Numbers: ACTG 026, 056-158, FDA 12E
Study First Received: November 2, 1999
Last Updated: March 11, 2011
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Meningitis
Injections, Intravenous
Cryptococcosis
Fluconazole
Administration, Oral
Acquired Immunodeficiency Syndrome
Amphotericin B

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Immunologic Deficiency Syndromes
Infection
Meningitis
Meningitis, Cryptococcal
Central Nervous System Diseases
Central Nervous System Fungal Infections
Central Nervous System Infections
Cryptococcosis
Immune System Diseases
Lentivirus Infections
Meningitis, Fungal
Mycoses
Nervous System Diseases
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Amphotericin B
Fluconazole
Liposomal amphotericin B
14-alpha Demethylase Inhibitors
Amebicides
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents

ClinicalTrials.gov processed this record on October 21, 2014