NCT00000708

Brief Summary

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for not_applicable

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Primary Completion

Last participant's last visit for primary outcome

July 1, 1991

Completed
8.3 years until next milestone

First Submitted

Initial submission to the registry

November 2, 1999

Completed
1.8 years until next milestone

First Posted

Study publicly available on registry

August 31, 2001

Completed
Last Updated

March 14, 2011

Status Verified

July 1, 1991

First QC Date

November 2, 1999

Last Update Submit

March 11, 2011

Conditions

Keywords

AIDS-Related Opportunistic InfectionsMeningitisInjections, IntravenousCryptococcus neoformansCryptococcosisDrug Therapy, CombinationFluconazoleAdministration, OralAcquired Immunodeficiency SyndromeAmphotericin B

Interventions

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • +9 more criteria

You may not qualify if:

  • 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.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Univ of Miami School of Medicine

Miami, Florida, 331361013, United States

Location

Tulane Univ School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Mem Sloan - Kettering Cancer Ctr

New York, New York, 10021, United States

Location

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, 10461, United States

Location

Univ of North Carolina

Chapel Hill, North Carolina, 275997215, United States

Location

Julio Arroyo

West Columbia, South Carolina, 29169, United States

Location

Related Publications (3)

  • Powderly WG. Recent advances in the management of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996 May;22 Suppl 2:S119-23. doi: 10.1093/clinids/22.supplement_2.s119.

    PMID: 8722838BACKGROUND
  • Powderly WG, Cloud GA, Dismukes WE, Saag MS. Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1994 May;18(5):789-92. doi: 10.1093/clinids/18.5.789.

    PMID: 8075272BACKGROUND
  • 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. doi: 10.1056/NEJM199201093260202.

    PMID: 1727236BACKGROUND

MeSH Terms

Conditions

Meningitis, CryptococcalHIV InfectionsAIDS-Related Opportunistic InfectionsMeningitisCryptococcosisAcquired Immunodeficiency Syndrome

Interventions

FlucytosineFluconazoleAmphotericin B

Condition Hierarchy (Ancestors)

Meningitis, FungalCentral Nervous System Fungal InfectionsMycosesBacterial Infections and MycosesInfectionsCentral Nervous System InfectionsCentral Nervous System DiseasesNervous System DiseasesNeuroinflammatory DiseasesBlood-Borne InfectionsCommunicable DiseasesSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesOpportunistic InfectionsSlow Virus Diseases

Intervention Hierarchy (Ancestors)

CytosinePyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsTriazolesAzolesMacrolidesPolyketidesLactonesOrganic Chemicals

Study Officials

  • Armstrong D

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Primary Completion

July 1, 1991

Last Updated

March 14, 2011

Record last verified: 1991-07

Locations