Meningitis, CryptococcalPhase 3NCT00001017
Comparison of Fluconazole and Amphotericin B in the Treatment of Brain Infections in Patients With AIDS
A Phase 3 study testing Fluconazole and Amphotericin B in people with Meningitis, Cryptococcal and HIV Infections, run by Pfizer at 28 sites in United States.
Trial summary
To compare the safety and effectiveness of a new drug, fluconazole, with that of the usual therapy, amphotericin B, in the prevention of a relapse of cryptococcal meningitis (CM) in patients with AIDS who have been successfully treated for acute CM in the last 6 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Meningitis, Cryptococcal, HIV Infections
- What is being tested?
- Fluconazole and Amphotericin B
- How many people
- 330 participants
- Where
- 28 sitesUnited States
- Study dates
- Start not givento Jul 1991
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infection documented by antibody (ELISA on two occasions or ELISA with Western blot confirmation), p24 antigen testing, or recovery of HIV in culture.
- Prior Medication:
- Required:
- Minimum total dose of 15 mg/kg of amphotericin B (either alone or in combination with flucytosine) during primary therapy. End of primary therapy within 6 weeks of start of maintenance therapy.
- Allowed:
- Past or present antiviral therapy and prophylaxis for Pneumocystis carinii pneumonia (PCP).
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- Pfizer must be notified if the patient is receiving ganciclovir at entry. Allowed with amphotericin B to treat or prevent side effects.
- Antipyretics.
- Hydrocortisone.
- Meperidine.
Who cannot join
- Co-existing Condition:
- Patients with the following are excluded:
- Clinical evidence of acute or chronic meningitis other than cryptococcosis.
- Allergy or intolerance of imidazoles, azoles, or amphotericin B. Unable to take oral medications reliably.
- Patients with the following are excluded:
- Clinical evidence of acute or chronic meningitis other than cryptococcosis.
Show all 25Show fewer
- Allergy or intolerance of imidazoles, azoles, or amphotericin B.
- Prior Medication:
- Excluded for more than 7 days after initiation of primary therapy for cryptococcosis:
- Ketoconazole.
- Fluconazole.
- Itraconazole.
- Miconazole.
- Any other systemic imidazole or azole.
- Excluded:
- Intrathecal amphotericin B.
- Coumadin-type anticoagulants.
- Oral hypoglycemics.
- Barbiturates.
- Phenytoin.
- Immunostimulants.
- Investigational drug or approved (licensed) drugs for investigational indications.
- Prior Treatment:
- Excluded:
- Lymphocyte replacement.
Trial locations and contacts
28 sites in 1 country.
28 sites in 1 country
United States28 sites
Johns Hopkins Hosp
Baltimore, Maryland, 21287
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, 02114
Beth Israel Deaconess - West Campus
Boston, Massachusetts, 02215
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, 14215
Univ of North Carolina
Chapel Hill, North Carolina, 275997215
Holmes Hosp / Univ of Cincinnati Med Ctr
Cincinnati, Ohio, 452670405
Univ Hosp of Cleveland / Case Western Reserve Univ
Cleveland, Ohio, 44106
Ohio State Univ Hosp Clinic
Columbus, Ohio, 432101228
Duke Univ Med Ctr
Durham, North Carolina, 27710
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, 11373
Indiana Univ Hosp
Indianapolis, Indiana, 462025250
UCLA CARE Ctr
Los Angeles, California, 90095
Univ of Miami School of Medicine
Miami, Florida, 331361013
Louisiana State Univ School of Medicine
New Orleans, Louisiana, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, 70112
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, 10003
Bellevue Hosp / New York Univ Med Ctr
New York, New York, 10016
Cornell Univ Med Ctr
New York, New York, 10021
Mem Sloan - Kettering Cancer Ctr
New York, New York, 10021
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, 10025
Mount Sinai Med Ctr
New York, New York, 10029
Univ of Rochester Medical Center
Rochester, New York, 14642
SUNY - Stony Brook
Stony Brook, New York, 117948153
Jack Weiler Hosp / Bronx Municipal Hosp
The Bronx, New York, 10465
Montefiore Med Ctr / Bronx Municipal Hosp
The Bronx, New York, 10467
North Central Bronx Hosp / Bronx Municipal Hosp
The Bronx, New York, 10467
Bronx Veterans Administration / Mount Sinai Hosp
The Bronx, New York, 10468
Julio Arroyo
West Columbia, South Carolina, 29169
About this study
Official title: Comparison of Fluconazole (UK-49,858) and Amphotericin B for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome
To compare the safety and effectiveness of a new drug, fluconazole, with that of the usual therapy, amphotericin B, in the prevention of a relapse of cryptococcal meningitis (CM) in patients with AIDS who have been successfully treated for acute CM in the last 6 months.
Cryptococcal meningitis is a life-threatening infectious complication of AIDS. Because relapse after treatment occurs in over 50 percent of cases, chronic maintenance therapy with intravenous (IV) amphotericin B is usually given. However, amphotericin B is not always effective, has toxic effects, and must be given by the intravenous route. Fluconazole is an antifungal agent that can be given orally and has been shown to be effective against cryptococcal infections in animals and against acute CM in a few AIDS patients. Also, the side effects experienced by over 2000 patients or volunteers given fluconazole have seldom been severe enough to require withdrawal of the drug.
Read the detailed description
Cryptococcal meningitis is a life-threatening infectious complication of AIDS. Because relapse after treatment occurs in over 50 percent of cases, chronic maintenance therapy with intravenous (IV) amphotericin B is usually given. However, amphotericin B is not always effective, has toxic effects, and must be given by the intravenous route. Fluconazole is an antifungal agent that can be given orally and has been shown to be effective against cryptococcal infections in animals and against acute CM in a few AIDS patients. Also, the side effects experienced by over 2000 patients or volunteers given fluconazole have seldom been severe enough to require withdrawal of the drug.
Patients accepted in the trial are randomly assigned to fluconazole or amphotericin B. Fluconazole is given orally once a day and amphotericin B is given intravenously once a week. Dosages depend on body weight. Medications may be given with amphotericin B to prevent or reduce discomfort from associated side effects. Patients are treated for 12 months and may continue to receive antiviral therapy, radiation therapy for mucocutaneous Kaposi's sarcoma, or preventive therapy for Pneumocystis carinii pneumonia (PCP) during the study.
- Conditions
- Meningitis, Cryptococcal, HIV Infections
- Being tested
- Fluconazole, Amphotericin B
- Keywords
- AIDS-Related Opportunistic Infections, Meningitis, Injections, Intravenous, Cryptococcosis, Fluconazole, Administration, Oral, Acquired Immunodeficiency Syndrome, Amphotericin B
- Medical subject headings
- Meningitis, Cryptococcal, HIV Infections, AIDS-Related Opportunistic Infections, Meningitis, Cryptococcosis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluconazoleDrug
Amphotericin BDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Primary completionJul 1991
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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 PfizerThe 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 3
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Enrolment
- 330 participants
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Armstrong D, Study chairDismukes W, Study chairPowderly W, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001017
- Sponsor's protocol ID
- ACTG 026
- Other IDs
- 056-158, FDA 12E
- Status last verified
- Sep 2002
- First submitted
- 2 Nov 1999
- Last updated
- 14 Mar 2011
- Results posted
- No
Publications
Saag MS, Powderly WG, Cloud GA, Robinson P, Grieco MH, Sharkey PK, Thompson SE, Sugar AM, Tuazon CU, Fisher JF, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group. N Engl J Med. 1992 Jan 9;326(2):83-9. doi: 10.1056/NEJM199201093260202.
PubMed 1727236Powderly WG, Saag MS, Cloud GA, Robinson P, Meyer RD, Jacobson JM, Graybill JR, Sugar AM, McAuliffe VJ, Follansbee SE, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group. N Engl J Med. 1992 Mar 19;326(12):793-8. doi: 10.1056/NEJM199203193261203.
PubMed 1538722Powderly WG, Cloud GA, Dismukes WE, Saag MS. Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1994 May;18(5):789-92. doi: 10.1093/clinids/18.5.789.
PubMed 8075272McKinney RE Jr, Maha MA, Connor EM, Feinberg J, Scott GB, Wulfsohn M, McIntosh K, Borkowsky W, Modlin JF, Weintrub P, et al. A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group. N Engl J Med. 1991 Apr 11;324(15):1018-25. doi: 10.1056/NEJM199104113241503.
PubMed 1672443
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Fluconazole (UK-49,858) and Amphotericin B for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome
- ClinicalTrials.gov ID
- NCT00001017
- Acronym / sponsor ID
- ACTG 026
- Conditions
- Meningitis, Cryptococcal, HIV Infections
- Keywords
- AIDS-Related Opportunistic Infections, Meningitis, Injections, Intravenous, Cryptococcosis, Fluconazole, Administration, Oral, Acquired Immunodeficiency Syndrome, Amphotericin B
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 330 participants
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Jul 1991 (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.
To compare the safety and effectiveness of a new drug, fluconazole, with that of the usual therapy, amphotericin B, in the prevention of a relapse of cryptococcal meningitis (CM) in patients with AIDS who have been successfully treated for acute CM in the last 6 months.
Cryptococcal meningitis is a life-threatening infectious complication of AIDS. Because relapse after treatment occurs in over 50 percent of cases, chronic maintenance therapy with intravenous (IV) amphotericin B is usually given. However, amphotericin B is not always effective, has toxic effects, and must be given by the intravenous route. Fluconazole is an antifungal agent that can be given orally and has been shown to be effective against cryptococcal infections in animals and against acute CM in a few AIDS patients. Also, the side effects experienced by over 2000 patients or volunteers given fluconazole have seldom been severe enough to require withdrawal of the drug.
Detailed description
Cryptococcal meningitis is a life-threatening infectious complication of AIDS. Because relapse after treatment occurs in over 50 percent of cases, chronic maintenance therapy with intravenous (IV) amphotericin B is usually given. However, amphotericin B is not always effective, has toxic effects, and must be given by the intravenous route. Fluconazole is an antifungal agent that can be given orally and has been shown to be effective against cryptococcal infections in animals and against acute CM in a few AIDS patients. Also, the side effects experienced by over 2000 patients or volunteers given fluconazole have seldom been severe enough to require withdrawal of the drug.
Patients accepted in the trial are randomly assigned to fluconazole or amphotericin B. Fluconazole is given orally once a day and amphotericin B is given intravenously once a week. Dosages depend on body weight. Medications may be given with amphotericin B to prevent or reduce discomfort from associated side effects. Patients are treated for 12 months and may continue to receive antiviral therapy, radiation therapy for mucocutaneous Kaposi's sarcoma, or preventive therapy for Pneumocystis carinii pneumonia (PCP) during the study.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- HIV infection documented by antibody (ELISA on two occasions or ELISA with Western blot confirmation), p24 antigen testing, or recovery of HIV in culture.
- Minimum total dose of 15 mg/kg of amphotericin B (either alone or in combination with flucytosine) during primary therapy. End of primary therapy within 6 weeks of start of maintenance therapy.
- Allowed:
- Past or present antiviral therapy and prophylaxis for Pneumocystis carinii pneumonia (PCP).
- Pfizer must be notified if the patient is receiving ganciclovir at entry. Allowed with amphotericin B to treat or prevent side effects.
Key exclusion criteria (25 listed)
- Clinical evidence of acute or chronic meningitis other than cryptococcosis.
- Allergy or intolerance of imidazoles, azoles, or amphotericin B. Unable to take oral medications reliably.
- Clinical evidence of acute or chronic meningitis other than cryptococcosis.
- Allergy or intolerance of imidazoles, azoles, or amphotericin B.
- Ketoconazole.
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 |
|---|---|---|
| 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 14 Mar 2011.
- Background: PubMed 1727236Saag MS, Powderly WG, Cloud GA, Robinson P, Grieco MH, Sharkey PK, Thompson SE, Sugar AM, Tuazon CU, Fisher JF, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group. N Engl J Med. 1992 Jan 9;326(2):83-9. doi: 10.1056/NEJM199201093260202.
- Background: PubMed 1538722Powderly WG, Saag MS, Cloud GA, Robinson P, Meyer RD, Jacobson JM, Graybill JR, Sugar AM, McAuliffe VJ, Follansbee SE, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group. N Engl J Med. 1992 Mar 19;326(12):793-8. doi: 10.1056/NEJM199203193261203.
- Background: PubMed 8075272Powderly WG, Cloud GA, Dismukes WE, Saag MS. Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1994 May;18(5):789-92. doi: 10.1093/clinids/18.5.789.
- Background: PubMed 1672443McKinney RE Jr, Maha MA, Connor EM, Feinberg J, Scott GB, Wulfsohn M, McIntosh K, Borkowsky W, Modlin JF, Weintrub P, et al. A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group. N Engl J Med. 1991 Apr 11;324(15):1018-25. doi: 10.1056/NEJM199104113241503.
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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.
Armstrong D study chair
Dismukes W study chair
Powderly W study chair
28 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fluconazole and Amphotericin B in people with Meningitis, Cryptococcal and HIV Infections, run by Pfizer at 28 sites in United States.
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 10 inclusion and 25 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 14 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 NCT00001017, which also lists 4 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 14 Mar 2011.