Search / Trial NCT00000639

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

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

Apply for Trial

Trial Information

Current as of March 05, 2024

Completed

Keywords

Aids Related Opportunistic Infections Meningitis Cryptococcosis Drug Evaluation Drug Therapy, Combination Fluconazole Flucytosine Acquired Immunodeficiency Syndrome Amphotericin B Brain Diseases

Description

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. 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.

Gender

All

Eligibility 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.

Attachments

readout_NCT00000639_2024-03-05.pdf

4.5 MB

NCT00000639_study_protocol.pdf

4.5 MB

About company

The National Institute of Allergy and Infectious Diseases (NIAID, /ˈnaɪ.æd/) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's mission is to conduct basic and applied research to better understand, treat, and prevent infectious, immunologic, and allergic diseases.

Contacts

JC

Jennifer Cobb

Immunology at National Institute of Allergy and Infectious Diseases (NIAID)

Locations

Los Angeles, California, United States

San Francisco, California, United States

Miami, Florida, United States

Honolulu, Hawaii, United States

Chicago, Illinois, United States

Indianapolis, Indiana, United States

Indianapolis, Indiana, United States

New Orleans, Louisiana, United States

Boston, Massachusetts, United States

Boston, Massachusetts, United States

Boston, Massachusetts, United States

Saint Louis, Missouri, United States

Saint Louis, Missouri, United States

Buffalo, New York, United States

New York, New York, United States

New York, New York, United States

Rochester, New York, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Greensboro, North Carolina, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

People applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported

Reviews (48)

4.6

All reviews come from applied patients

5 stars
41
4 stars
6
3 stars
2
2 stars
0
1 stars
0
Leslie Alexander
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Michael Foster
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Dries Vincent
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Leslie Alexander
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Discussion 0