A Study of Fluconazole in the Treatment of Cryptococcal Meningitis in Patients With AIDS

HIV Infections Clinical Trial

Official title:

Double Blind Placebo Controlled Study of Fluconazole (UK-49,858) for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002294
• Other study ID #: 012A
• Secondary ID: 056-114A
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: December 1989
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To compare the safety and effectiveness of fluconazole with that of placebo as maintenance treatment for preventing the relapse of cryptococcal meningitis in patients with AIDS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiviral therapy (e.g., zidovudine).

• Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia (PCP).

Concurrent Treatment:

Allowed:

• Radiation therapy for mucocutaneous Kaposi's sarcoma.

Patients must be oriented to person, place, and time and able to give written informed consent.

• Patients must have had an acute episode of cryptococcal meningitis that was documented by recovery and identification of cryptococcus from lumbar cerebrospinal fluid (CSF) culture within 4 months of study entry.

• Adequate therapy will consist of 6 - 16 weeks of treatment with amphotericin B alone, amphotericin B + oral flucytosine, or a period of the combination followed by amphotericin alone. Adequate regimens will include:

• A minimum total amphotericin B dose of 2 grams as monotherapy.

• 6 weeks of flucytosine at 150 mg/kg/day (or levels of 20 to 100 mcg/ml demonstrated) plus amphotericin B at an average daily dose of at least 0.3 mg/kg/day or to a total dose of 1 gram.

• After a shorter period of the combination amphotericin/flucytosine therapy, an additional Y grams of amphotericin B monotherapy will make therapy adequate where Y = 2 gm-(X weeks combination therapy / 3 weeks).

• For example, a patient who received 3 weeks of combination followed by amphotericin alone would need an additional 2 gm - 3 weeks/3 weeks = 1 gm of amphotericin B.

• Patients need not be receiving amphotericin B at the time of randomization but must begin study maintenance therapy within 3 weeks of cessation of primary amphotericin B therapy.

Prior Medication:

Allowed:

• Antiviral therapy (e.g., zidovudine (AZT)).

• Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia (PCP).

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Clinical evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis.

• History of allergy or intolerance of imidazoles, azoles, or amphotericin B.

• Moderate or severe liver disease.

Concurrent Medication:

Excluded:

• Intrathecal amphotericin B.

• Coumarin-type anticoagulants.

• Oral hypoglycemics.

• Barbiturates.

• Phenytoin.

• Immunostimulants.

• Investigational drugs or approved (licensed) drugs for investigational indications.

Concurrent Treatment:

Excluded:

• Lymphocyte replacement.

Patients with the following are excluded:

• Clinical evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis.

• History of allergy or intolerance of imidazoles, azoles, or amphotericin B.

• Moderate or severe liver disease defined by specific lab values.

• Inability to take oral medications reliably.

Prior Medication:

Excluded:

• Intrathecal amphotericin B.

• Coumarin-type anticoagulants.

• Oral hypoglycemics.

• Barbiturates.

• Phenytoin.

• Immunostimulants.

• Investigational drugs or approved (licensed) drugs for investigational indications.

Prior Treatment:

Excluded:

• Lymphocyte replacement.

Study Design

Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• Fluconazole

Locations

Country	Name	City	State
United States	Dr Robert Larsen	Los Angeles	California
United States	UCI Med Ctr	Orange	California
United States	UCSD	San Diego	California
United States	Dr Paul Rothman	Sherman Oaks	California
United States	Stanford Univ School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States,