Meningitis, CryptococcalNCT00000639

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

A study testing Itraconazole, Flucytosine and Fluconazole in people with Meningitis, Cryptococcal and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 24 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 13 years and older
Conditions the study is for: Meningitis, Cryptococcal, HIV Infections
What is being tested?: Itraconazole, Flucytosine and Fluconazole
How many people: 400 participants
Where: 24 sitesUnited States
Study dates: Start not givento Sep 1997
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 13 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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.

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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.

Trial locations and contacts

24 sites in 1 country.

City, postcode or hospital

24 sites in 1 country

United States24 sites

Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, 02114
Bmc Actg Crs
Boston, Massachusetts, 02118
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215
Unc Aids Crs
Chapel Hill, North Carolina, 27599
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, North Carolina
Northwestern University CRS
Chicago, Illinois, 60611
Univ. of Cincinnati CRS
Cincinnati, Ohio, 45267
The Ohio State Univ. AIDS CRS
Columbus, Ohio, 43210
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, 27401
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202
Methodist Hosp. of Indiana
Indianapolis, Indiana, 46202
USC CRS
Los Angeles, California, 90033
Univ. of Miami AIDS CRS
Miami, Florida, 33136
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, 70112
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, 10003
Cornell University A2201
New York, New York, 10021
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104
Pitt CRS
Pittsburgh, Pennsylvania, 15213
Univ. of Rochester ACTG CRS
Rochester, New York, 14642
Ucsf Aids Crs
San Francisco, California, 94110
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri
Washington U CRS
St Louis, Missouri

Other trials in United States

About this study

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.

Read the 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.

Conditions: Meningitis, Cryptococcal, HIV Infections
Being tested: Itraconazole, Flucytosine, Fluconazole, Amphotericin B
Keywords: AIDS-Related Opportunistic Infections, Meningitis, Cryptococcosis, Drug Evaluation, Drug Therapy, Combination, Fluconazole, Flucytosine, Acquired Immunodeficiency Syndrome, Amphotericin B, Brain Diseases
Medical subject headings: Meningitis, Cryptococcal, HIV Infections, AIDS-Related Opportunistic Infections, Meningitis, Cryptococcosis, Acquired Immunodeficiency Syndrome, Brain Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ItraconazoleDrug
FlucytosineDrug
FluconazoleDrug
Amphotericin BDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

?Sep 1997

First posted31 Aug 2001 (estimated)
Study completionSep 1997

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Meningitis, CryptococcalStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Masking: Double blind
Enrolment: 400 participants

IDs, dates and publications

ClinicalTrials.gov ID: NCT00000639
Sponsor's protocol ID: ACTG 159
Other IDs: FDA 235A, MSG Study 17, 11134
Status last verified: Oct 2021
First submitted: 2 Nov 1999
Last updated: 2 Nov 2021
Results posted: No

Publications

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.
PubMed 9203426
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.
PubMed 8722838
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)

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Fungal Infection Susceptibility
Cryptococcal Infection, Cryptococcal Pneumonia
RecruitingObservational study
Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Idiopathic CD4+ Lymphocytopenia, Cryptococcal Meningitis
Not yet recruitingPhase 3
Optimizing Care for Cryptococcal Antigenemia: Evaluation of Short Course Fluconazole and ART Timing Among CrAg+ Persons With Low Titers
Cryptococcal Antigenemia, HIV-1-infection
RecruitingPhase 2/3
Platform Trial For Cryptococcal Meningitis (PLATFORM-CM)
Hiv, Cryptococcal Meningitis
RecruitingPhase 2/3
Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia
Cryptococcal Meningitis

All Meningitis, Cryptococcal trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00000639
Acronym / sponsor ID: ACTG 159
Conditions: Meningitis, Cryptococcal, HIV Infections
Keywords: AIDS-Related Opportunistic Infections, Meningitis, Cryptococcosis, Drug Evaluation, Drug Therapy, Combination, Fluconazole, Flucytosine, Acquired Immunodeficiency Syndrome
Study type: Interventional
Recruitment status: Completed
Enrolment: 400 participants
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: Washington University School of Medicine
Study completion: Sep 1997 (actual)
First posted: 31 Aug 2001 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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.

Study design

Primary purpose: Treatment
Masking: Double blind

Who may qualify

Ages: 13 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (21 listed)

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).

Key exclusion criteria (23 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Itraconazole	Drug	–
Flucytosine	Drug	–
Fluconazole	Drug	–
Amphotericin B	Drug	–

Primary outcome

Not reported in the source record.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
Background: PubMed 9203426van 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.
Background: PubMed 8722838Powderly 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.
BackgroundPowderly 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)

Related trials for Meningitis, Cryptococcal

RecruitingObservational study
Fungal Infection Susceptibility
Cryptococcal Infection, Cryptococcal Pneumonia
RecruitingObservational study
Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Idiopathic CD4+ Lymphocytopenia, Cryptococcal Meningitis
Not yet recruitingPhase 3
Optimizing Care for Cryptococcal Antigenemia: Evaluation of Short Course Fluconazole and ART Timing Among CrAg+ Persons With Low Titers
Cryptococcal Antigenemia, HIV-1-infection
RecruitingPhase 2/3
Platform Trial For Cryptococcal Meningitis (PLATFORM-CM)
Hiv, Cryptococcal Meningitis
RecruitingPhase 2/3
Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia
Cryptococcal Meningitis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

van der Horst C study chair

Saag M study chair

24 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00000639, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2021.