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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00000708
• Date of registration: 02/11/1999
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Multi-center Comparison of Fluconazole (UK-49,858) and Amphotericin B as Treatment for Acute Cryptococcal Meningitis
• Scientific title: Multi-center Comparison of Fluconazole (UK-49,858) and Amphotericin B as Treatment for Acute Cryptococcal Meningitis
• Date of first enrolment: July 2000
• Target sample size: 120
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00000708
• Study type: Interventional
• Study design: Intervention Model: Parallel Assignment, Primary Purpose: Treatment
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: Armstrong D

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

HIV Infections

Meningitis, Cryptococcal

Intervention(s)

Drug: Flucytosine

Drug: Fluconazole

Drug: Amphotericin B

Secondary ID(s)

ACTG 059

Project 056

Investigator 556

Protocol 159

Source(s) of Monetary Support

Please refer to primary and secondary sponsors