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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00002294

Collaborator

(none)

Locations

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Meningitis, Cryptococcal HIV Infections	Drug: Fluconazole	N/A

Study Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 0 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dr Robert Larsen	Los Angeles	California	United States	90033
2	UCI Med Ctr	Orange	California	United States	92668
3	UCSD	San Diego	California	United States	92103
4	Dr Paul Rothman	Sherman Oaks	California	United States	91403
5	Stanford Univ School of Medicine	Stanford	California	United States	94305