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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00000639
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : March 30, 2012
Sponsor:
Collaborator:
Washington University School of Medicine
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.


Condition or disease Intervention/treatment Phase
Meningitis, Cryptococcal HIV Infections Drug: Itraconazole Drug: Flucytosine Drug: Fluconazole Drug: Amphotericin B Not Applicable

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 400 participants
Masking: Double
Primary Purpose: Treatment
Official 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
Actual Study Completion Date : September 1997






Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   13 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000639


Locations
Show Show 24 study locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Washington University School of Medicine
Investigators
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Study Chair: van der Horst C
Study Chair: Saag M
Publications:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000639    
Other Study ID Numbers: ACTG 159
FDA 235A
MSG Study 17
11134 ( Registry Identifier: DAIDS ES Registry Number )
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: March 30, 2012
Last Verified: March 2012
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Meningitis
Cryptococcosis
Drug Evaluation
Drug Therapy, Combination
Fluconazole
Flucytosine
Acquired Immunodeficiency Syndrome
Amphotericin B
Brain Diseases
Additional relevant MeSH terms:
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Meningococcal Infections
Meningitis, Cryptococcal
Meningitis
Central Nervous System Diseases
Nervous System Diseases
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Meningitis, Fungal
Central Nervous System Fungal Infections
Mycoses
Cryptococcosis
Central Nervous System Infections
Itraconazole
Fluconazole
Amphotericin B
Liposomal amphotericin B
Flucytosine
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors