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Comparison of Fluconazole and Amphotericin B in the Treatment of Brain Infections in Patients With AIDS
This study has been completed.
First Received: November 2, 1999   Last Updated: July 28, 2008   History of Changes
Sponsors and Collaborators: Pfizer
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001017
  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 III

Study Type: Interventional
Study Design: Treatment, Parallel Assignment
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
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
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
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
Louisiana State 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
SUNY - Stony Brook
Stony Brook, New York, United States, 117948153
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Cornell Univ Med Ctr
New York, New York, United States, 10021
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Mount Sinai Med Ctr
New York, New York, United States, 10029
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
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
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, United States, 10003
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
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
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
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
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:
Study ID Numbers: ACTG 026, 056-158, FDA 12E
Study First Received: November 2, 1999
Last Updated: July 28, 2008
ClinicalTrials.gov Identifier: NCT00001017     History of Changes
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

Study placed in the following topic categories:
Fluconazole
Abelcet
Amphotericin B
Opportunistic Infections
Meningitis, Fungal
Sexually Transmitted Diseases, Viral
Acquired Immunodeficiency Syndrome
Central Nervous System Diseases
Liposomal amphotericin B
Immunologic Deficiency Syndromes
Meningitis
Virus Diseases
Anti-Bacterial Agents
Mycoses
Central Nervous System Infections
HIV Infections
Antifungal Agents
AIDS-Related Opportunistic Infections
Sexually Transmitted Diseases
Meningitis, Cryptococcal
Central Nervous System Fungal Infections
Cryptococcosis
Retroviridae Infections

Additional relevant MeSH terms:
Abelcet
Anti-Infective Agents
Communicable Diseases
Antiprotozoal Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Infection
Liposomal amphotericin B
Meningitis
Anti-Bacterial Agents
Mycoses
Antiparasitic Agents
Antifungal Agents
Therapeutic Uses
Antibiotics, Antifungal
Meningitis, Cryptococcal
Amebicides
Central Nervous System Fungal Infections
Retroviridae Infections
Fluconazole
Amphotericin B
RNA Virus Infections
Meningitis, Fungal
Immune System Diseases
Acquired Immunodeficiency Syndrome
Nervous System Diseases
Central Nervous System Diseases
Pharmacologic Actions
Immunologic Deficiency Syndromes
Virus Diseases

ClinicalTrials.gov processed this record on July 02, 2009