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Meningitis, CryptococcalNCT00000708

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

A study testing Flucytosine, Fluconazole and Amphotericin B in people with Meningitis, Cryptococcal and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Meningitis, Cryptococcal, HIV Infections
What is being tested?
Flucytosine, Fluconazole and Amphotericin B
How many people
120 participants
Where
6 sitesUnited States
Study dates
Start not givento Jul 1991
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Univ of North Carolina

    Chapel Hill, North Carolina, 275997215

  • Univ of Miami School of Medicine

    Miami, Florida, 331361013

  • Tulane Univ School of Medicine

    New Orleans, Louisiana, 70112

  • Mem Sloan - Kettering Cancer Ctr

    New York, New York, 10021

  • Bronx Municipal Hosp Ctr/Jacobi Med Ctr

    The Bronx, New York, 10461

  • Julio Arroyo

    West Columbia, South Carolina, 29169

Other trials in United States

About this study

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.

Read the 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.

Being tested
Flucytosine, Fluconazole, Amphotericin B
Keywords
AIDS-Related Opportunistic Infections, Meningitis, Injections, Intravenous, Cryptococcus neoformans, Cryptococcosis, Drug Therapy, Combination, Fluconazole, Administration, Oral, Acquired Immunodeficiency Syndrome, Amphotericin B
Medical subject headings
Meningitis, Cryptococcal, HIV Infections, AIDS-Related Opportunistic Infections, Meningitis, Cryptococcosis, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FlucytosineDrug

  • FluconazoleDrug

  • Amphotericin BDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Primary completionJul 1991

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Intervention model
Parallel groups
Enrolment
120 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000708
Sponsor's protocol ID
ACTG 059
Other IDs
Protocol 159, Project 056, Investigator 556
Status last verified
Jul 1991
First submitted
2 Nov 1999
Last updated
14 Mar 2011
Results posted
No

Publications

  • 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.

    PubMed 8722838

  • 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.

    PubMed 8075272

  • 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.

    PubMed 1727236

Questions about this trial

What is this clinical trial studying?

A study testing Flucytosine, Fluconazole and Amphotericin B in people with Meningitis, Cryptococcal and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00000708, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2011.

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