A Randomized Double Blind Protocol Comparing Amphotericin B With Flucytosine to Amphotericin B Alone Followed by a Comparison of Fluconazole and Itraconazole in the Treatment of Acute Cryptococcal Meningitis

• Register: ClinicalTrials.gov
• Last refreshed on: 8 November 2021
• Main ID: NCT00000639
• Date of registration: 02/11/1999
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: A Randomized Double Blind Protocol Comparing Amphotericin B With Flucytosine to Amphotericin B Alone Followed by a Comparison of Fluconazole and Itraconazole in the Treatment of Acute Cryptococcal Meningitis
• Scientific title: A Randomized Double Blind Protocol Comparing Amphotericin B With Flucytosine to Amphotericin B Alone Followed by a Comparison of Fluconazole and Itraconazole in the Treatment of Acute Cryptococcal Meningitis
• Target sample size: 400
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00000639
• Study type: Interventional
• Study design: Primary purpose: Treatment. Masking: Double.
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: van der Horst C

• Name: Saag M

Key inclusion & exclusion criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

- Interruption of myelosuppressive therapies and/or administration of erythropoietin, at
discretion of investigator, to maintain hemoglobin = or > 7 g/dl.

- Adjunctive corticosteroids may be administered during the triazole phase for patients
who develop Pneumocystis carinii pneumonia and meet the prescribed criteria.

- Hydrocortisone, not to exceed 50 mg/day, during the amphotericin phase.

- Aerosolized pentamidine or systemic chemoprophylaxis for Pneumocystis carinii
pneumonia should be given to all patients with a CD4 count < 200 cells/mm3.

- Antiretroviral drugs (including zidovudine (AZT), didanosine (ddI), dideoxycytidine
(ddC)) after patient has tolerated oral triazole for one week (after 3 weeks of study
treatment).

- Maintenance treatment (except for rifamycins) for other opportunistic infections such
as cytomegalovirus (CMV) retinitis, cerebral toxoplasmosis or mycobacterial
infections, provided that their hematologic and hepatic values are stable and they
meet the entry criteria.

Concurrent Treatment:

Allowed:

- Transfusion, at discretion of investigator, to maintain hemoglobin = or > 7 g/dl.

Patients must have:

- HIV infection.

- Primary episode of acute cryptococcal meningitis.

- Willing to participate in the study for a full 10 weeks and either be able to give
informed consent or have a family member or guardian able to give informed consent.

Prior Medication:

Allowed:

Fluconazole prophylaxis, not exceeding 200 mg/day.

Risk Behavior:

Allowed:

- History of high-risk behavior for HIV infection (bisexual or homosexual men, intravenous
drug abusers) and their sexual partners.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

- Inability to take oral medication (if necessary, flucytosine and flucytosine placebo
may be administered via nasogastric tube during the amphotericin phase).

- History of hypersensitivity to imidazole or triazole compounds.

- Active hepatitis (viral, drug-induced, or other) defined by progressive worsening of
hepatic enzymes to grade 3 or 4 toxicity on at least two occasions.

- Comatose.

- Concurrent CNS disease which, in the opinion of the investigator, would interfere with
assessment of response.

Concurrent Medication:

Excluded:

- Continued treatment with H2 blockers (ranitidine (Zantac), cimetidine (Tagamet),
omeprazole (Prilosec), nizatidine (Axid), famotidine (Pepcid)).

- Antacids and didanosine (ddI) within 2 hours of triazole administration.

- Rifampin, rifabutin (Ansamycin), and other rifamycin derivatives, phenytoin
(Dilantin), phenobarbital, or carbamazepine (Tegretol).

- Other systemic antifungal agents.

Prior Medication:

Excluded:

- Amphotericin, > 1 mg/kg, or fluconazole or ketoconazole, > 1200 mg, as prior treatment
for current primary episode of acute cryptococcal meningitis or treatment started for
this episode more than 72 hours prior to enrollment into study.

- Phenytoin (Dilantin), carbamazepine (Tegretol), phenobarbital, rifabutin (Ansamycin),
rifampin or other rifamycins within the last 15 days.

Patients may not have:

- Inability to take oral medication (if necessary, flucytosine and flucytosine placebo
may be administered via nasogastric tube during the amphotericin phase).

- History of hypersensitivity to imidazole or triazole compounds.

- Active hepatitis.

- Patients who are comatose.

- Concurrent CNS disease which, in the opinion of the investigator, would interfere with
assessment of response.



Age minimum: 13 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HIV Infections

Meningitis, Cryptococcal

Intervention(s)

Drug: Itraconazole

Drug: Fluconazole

Drug: Amphotericin B

Drug: Flucytosine

Secondary ID(s)

ACTG 159

11134

FDA 235A

MSG Study 17

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Washington University School of Medicine