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

NCT ID: NCT00002113

Last Updated: 2005-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL

Brief 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.

Detailed 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.

Conditions

Meningitis, Cryptococcal; HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

Flucytosine

Intervention Type: DRUG

Fluconazole

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Locations

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, United States

Countries

United States

References

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. doi: 10.1093/clinids/19.4.741.

Reference Type: BACKGROUND

PMID: 7803641 (View on PubMed)

Other Identifiers

R-0202

Identifier Type: -

Identifier Source: secondary_id

213A

Identifier Type: -

Identifier Source: org_study_id