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
NCT ID: NCT00000639
Last Updated: 2021-11-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
400 participants
INTERVENTIONAL
1997-09-30
Brief Summary
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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.
Detailed Description
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Patients are selected by a randomization process to take amphotericin B intravenously (in the vein), for 14 days, and either placebo (ineffective substance) or flucytosine for 14 days. Then patients are again selected by a randomization process to take either (1) fluconazole for a total of 8 weeks plus itraconazole placebo; or (2) itraconazole for a total of 8 weeks plus fluconazole placebo.
Conditions
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Keywords
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Study Design
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TREATMENT
DOUBLE
Interventions
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Itraconazole
Flucytosine
Fluconazole
Amphotericin B
Eligibility Criteria
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Inclusion Criteria
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
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.
13 Years
ALL
No
Sponsors
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Washington University School of Medicine
OTHER
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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van der Horst C
Role: STUDY_CHAIR
Saag M
Role: STUDY_CHAIR
Locations
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USC CRS
Los Angeles, California, United States
Ucsf Aids Crs
San Francisco, California, United States
Univ. of Miami AIDS CRS
Miami, Florida, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States
Northwestern University CRS
Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States
Bmc Actg Crs
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 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, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States
Cornell University A2201
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Unc Aids Crs
Chapel Hill, North Carolina, 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, United States
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States
Pitt CRS
Pittsburgh, Pennsylvania, United States
Countries
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References
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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.
Powderly 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.
Powderly 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)
Other Identifiers
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FDA 235A
Identifier Type: -
Identifier Source: secondary_id
MSG Study 17
Identifier Type: -
Identifier Source: secondary_id
11134
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG 159
Identifier Type: -
Identifier Source: org_study_id