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

March 11, 2011 updated by: Pfizer

Comparison of Fluconazole (UK-49,858) and Amphotericin B for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

330

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Parallel Assignment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Armstrong D
  • Study Chair: Dismukes W
  • Study Chair: Powderly W

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Primary Completion (Actual)

July 1, 1991

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

March 14, 2011

Last Update Submitted That Met QC Criteria

March 11, 2011

Last Verified

September 1, 2002

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 026
  • 056-158
  • FDA 12E

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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