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
4 other identifiers
interventional
400
1 country
24
Brief Summary
To evaluate the effectiveness and safety of amphotericin B plus flucytosine (5-fluorocytosine) compared to amphotericin B alone for a first episode of acute cryptococcal meningitis in AIDS patients, and to compare the effectiveness and safety of fluconazole versus itraconazole. At least 10 percent of patients with a low CD4 count and HIV infection will develop meningitis due to Cryptococcus neoformans. More effective treatments than the standard therapy need to be explored.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Completion
Last participant's last visit for all outcomes
September 1, 1997
CompletedFirst Submitted
Initial submission to the registry
November 2, 1999
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedNovember 2, 2021
October 1, 2021
November 2, 1999
October 26, 2021
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- 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.
- +6 more criteria
You may not qualify if:
- 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:
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
USC CRS
Los Angeles, California, 90033, United States
Ucsf Aids Crs
San Francisco, California, 94110, United States
Univ. of Miami AIDS CRS
Miami, Florida, 33136, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States
Northwestern University CRS
Chicago, Illinois, 60611, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, 46202, United States
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, 70112, United States
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, 02114, United States
Bmc Actg Crs
Boston, Massachusetts, 02118, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215, United States
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St Louis, Missouri, United States
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, 10003, United States
Cornell University A2201
New York, New York, 10021, United States
Univ. of Rochester ACTG CRS
Rochester, New York, 14642, United States
Unc Aids Crs
Chapel Hill, North Carolina, 27599, United States
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, North Carolina, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, 27401, United States
Univ. of Cincinnati CRS
Cincinnati, Ohio, 45267, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, 43210, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104, United States
Pitt CRS
Pittsburgh, Pennsylvania, 15213, United States
Related Publications (3)
van der Horst CM, Saag MS, Cloud GA, Hamill RJ, Graybill JR, Sobel JD, Johnson PC, Tuazon CU, Kerkering T, Moskovitz BL, Powderly WG, Dismukes WE. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group. N Engl J Med. 1997 Jul 3;337(1):15-21. doi: 10.1056/NEJM199707033370103.
PMID: 9203426BACKGROUNDPowderly WG. Recent advances in the management of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996 May;22 Suppl 2:S119-23. doi: 10.1093/clinids/22.supplement_2.s119.
PMID: 8722838BACKGROUNDPowderly WG, Tuazon C, Cloud GA, Saag MS, Van Der Horst C. Serum and CSF cryptococcal antigen in management of cryptococcal meningitis in AIDS. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:66 (abstract no 6)
BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
van der Horst C
- STUDY CHAIR
Saag M
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Masking
- DOUBLE
- Purpose
- TREATMENT
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 1999
First Posted
August 31, 2001
Study Completion
September 1, 1997
Last Updated
November 2, 2021
Record last verified: 2021-10