Multi-center Comparison of Fluconazole (UK-49,858) and Amphotericin B as Treatment for Acute Cryptococcal Meningitis

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000708
First received: November 2, 1999
Last updated: March 11, 2011
Last verified: July 1991
  Purpose

To compare the safety and effectiveness of fluconazole (FCZ) and amphotericin B (AMB), alone or in combination with flucytosine (FLC), as treatment for acute cryptococcal meningitis in patients who have not been treated previously or who have relapsed after a previous successful treatment.

Cryptococcal meningitis is an important cause of disease and death among patients with AIDS. Usually AMB is given either alone or with FLC to patients with this infection, but these treatments are not always effective and both have toxic effects. Animal studies and preliminary studies in humans show that FCZ is active in cryptococcal meningitis and suggest that it may be less toxic than either AMB or FLC.


Condition Intervention
Meningitis, Cryptococcal
HIV Infections
Drug: Flucytosine
Drug: Fluconazole
Drug: Amphotericin B

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Multi-center Comparison of Fluconazole (UK-49,858) and Amphotericin B as Treatment for Acute Cryptococcal Meningitis

Resource links provided by NLM:


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

Estimated Enrollment: 120
Primary Completion Date: July 1991 (Final data collection date for primary outcome measure)
Detailed Description:

Cryptococcal meningitis is an important cause of disease and death among patients with AIDS. Usually AMB is given either alone or with FLC to patients with this infection, but these treatments are not always effective and both have toxic effects. Animal studies and preliminary studies in humans show that FCZ is active in cryptococcal meningitis and suggest that it may be less toxic than either AMB or FLC.

Patients accepted into the study are randomly assigned to FCZ or AMB. Patients assigned to FCZ take FCZ by mouth daily for 10 weeks. Patients assigned to AMB are given intravenous injections of AMB daily for 6-10 weeks. Non-AIDS patients assigned to AMB also take FLC by mouth daily. The use of FLC in patients with AIDS is decided on an individual basis. Patients with AIDS who respond satisfactorily to FCZ receive maintenance therapy to prevent relapse for an additional 12 months. Patients with AIDS who respond to AMB may qualify for another Pfizer Central Research protocol. Patients without AIDS who respond to therapy are observed for 6 months for relapse. During therapy, samples of blood and cerebrospinal fluid (by lumbar puncture) are taken periodically in order to evaluate the effectiveness of the drug treatments and to identify possible toxic effects.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Immunosuppressant therapy.
  • Cyclosporin plasma concentrations should be monitored and appropriate dosage adjustments made when used with amphotericin B or fluconazole.
  • Antiviral therapy.
  • Prophylaxis for Pneumocystis carinii pneumonia.
  • Treatment of intercurrent opportunistic infection as long as no investigational agent, or approved agent for an investigational indication, is used.
  • Antipyretics, hydrocortisone, or meperidine to prevent or ameliorate side effects associated with amphotericin B.

Concurrent Treatment:

Allowed:

- Radiation therapy for mucocutaneous Kaposi's sarcoma.

Patients must have:

  • Written informed consent obtained from the patient or from the patient's legal guardian.
  • One of the following:
  • (1) Tentative identification of Cryptococcus neoformans in culture of lumbar cerebrospinal fluid (CSF). Results of baseline cultures need not be available when therapy is begun, but therapy is discontinued if the baseline CSF culture is later found to be negative for C. neoformans, or (2) Clinical and CSF findings (cell count, protein, glucose) compatible with cryptococcal meningitis plus one of the following:
  • (a) Positive CSF India ink examination, (b) Culture or biopsy evidence of extraneural cryptococcal infection, (c) Positive serum of CSF cryptococcal antigen test, or increase in titer for previously treated patients with suspected relapse, or (d) Biopsy evidence of central nervous system cryptococcal infection.
  • Treatment status of either no prior systemic antifungal therapy for cryptococcosis or relapse after prior therapy. The success of prior therapy must have been documented by negative CSF culture at the end of therapy.

Prior Medication:

Allowed within 4 weeks of study entry:

- Successful prior therapy for cryptococcosis, but no more than 1 mg/kg/week amphotericin B.

Allowed:

  • Immunosuppressant therapy.
  • Antiviral therapy.
  • Prophylaxis for Pneumocystis carinii pneumonia.

Exclusion Criteria

Co-existing Condition:

Excluded:

  • Acute or chronic meningitis based on any etiology other than cryptococcosis.
  • History of allergy to or intolerance of imidazoles, or amphotericin B.
  • Moderate or severe liver disease defined as any one or more of the following:
  • SGOT or SGPT > 5 x upper limit of normal, total bilirubin > 2.5 mg/dl, prothrombin time > 5 seconds over control, or alkaline phosphatase > 2 x upper limit of normal.
  • Comatose patients.

Concurrent Medication:

Excluded:

  • Drugs with low therapeutic ratios that undergo hepatic metabolism may not be used with fluconazole until possible drug interactions have been clarified.
  • Coumarin-type anticoagulants.
  • Oral hypoglycemics.
  • Barbiturates.
  • Immunostimulants.
  • Investigational drugs or approved (licensed) drugs for investigational indications.
  • Systemic antifungal agent other than the assigned study drug.

Concurrent Treatment:

Excluded:

Lymphocyte replacement.

Prior Medication:

Excluded within 4 weeks of study entry:

  • More than 1 mg/kg/week amphotericin B.

Patients unlikely to survive more than 2 weeks.

  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: NCT00000708

Locations
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Louisiana
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, New York
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
Sponsors and Collaborators
Investigators
Study Chair: Armstrong D
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00000708     History of Changes
Other Study ID Numbers: ACTG 059, Protocol 159, Project 056, Investigator 556
Study First Received: November 2, 1999
Last Updated: March 11, 2011
Health Authority: United States: Federal Government

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

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

ClinicalTrials.gov processed this record on August 21, 2014