A Pilot Study of Fluconazole Plus Flucytosine for the Treatment of AIDS Patients With Acute Cryptococcal Meningitis.

HIV Infections Clinical Trial

Official title:

A Pilot Study of Fluconazole Plus Flucytosine for the Treatment of AIDS Patients With Acute Cryptococcal Meningitis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002113
• Other study ID #: 213A
• Secondary ID: R-0202
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: April 1996
• 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 evaluate and estimate the safety and efficacy of the combination of fluconazole and flucytosine as treatment for acute cryptococcal meningitis in patients with AIDS.

Fluconazole and flucytosine have different mechanisms of action. Since fluconazole has not been associated with hematologic suppression and does not produce renal impairment that can result in higher serum flucytosine levels, this combination may be better tolerated than is amphotericin B plus flucytosine.

Description:

Fluconazole and flucytosine have different mechanisms of action. Since fluconazole has not been associated with hematologic suppression and does not produce renal impairment that can result in higher serum flucytosine levels, this combination may be better tolerated than is amphotericin B plus flucytosine.

Patients in each cohort receive a lower dose of fluconazole alone or in combination with flucytosine, or a higher dose of fluconazole alone. Doses in subsequent cohorts are escalated if safety data in the previous cohort is satisfactory. Patients are evaluated weekly for the first 4 weeks and every 2 weeks thereafter. Therapy continues until 8 weeks after the CSF becomes culture negative, up to a maximum of 26 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiviral therapy (AZT, DHPG).

• Prophylaxis for Pneumocystis carinii pneumonia.

• Treatment for intercurrent opportunistic infection.

Concurrent Treatment:

Allowed:

• Radiation therapy for mucocutaneous Kaposi's sarcoma.

Patients must have:

• AIDS.

• Evidence of Cryptococcal neoformans in culture or lumbar CSF OR clinical and CSF findings compatible with cryptococcal meningitis.

• No evidence of acute or chronic meningitis of any etiology other than cryptococcosis.

• Life expectancy of at least 2 weeks.

Prior Medication:

Allowed:

• Prior antiviral therapy (AZT, DHPG).

• Prophylaxis for Pneumocystis carinii pneumonia.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Relapsing on maintenance triazole therapy for cryptococcal meningitis.

• Unable to take oral medication.

Concurrent Medication:

Excluded:

• Concomitant use of any antifungal agent other than study drug.

Patients with the following prior conditions are excluded:

History of allergy to or intolerance of imidazoles, azoles, or flucytosine.

Prior Medication:

Excluded:

• More than 1 mg/kg amphotericin B.

• Systemic antifungal agents within 7 days prior to study entry.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• Flucytosine

• Fluconazole

Locations

Country	Name	City	State
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCI Med Ctr	Orange	California
United States	UCSD Med Ctr - Owen Clinic	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (1)

Larsen RA, Bozzette SA, Jones BE, Haghighat D, Leal MA, Forthal D, Bauer M, Tilles JG, McCutchan JA, Leedom JM. Fluconazole combined with flucytosine for treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1994 Oct;19(4):741-5. — View Citation