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Comparison of Fluconazole and Amphotericin B in the Treatment of Brain Infections in Patients With AIDS

Primary Purpose

Meningitis, Cryptococcal, HIV Infections

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Fluconazole
Amphotericin B
Sponsored by
Pfizer
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Meningitis, Cryptococcal focused on measuring AIDS-Related Opportunistic Infections, Meningitis, Injections, Intravenous, Cryptococcosis, Fluconazole, Administration, Oral, Acquired Immunodeficiency Syndrome, Amphotericin B

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria 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). 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. Exclusion Criteria 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. 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.

Sites / Locations

  • UCLA CARE Ctr
  • Univ of Miami School of Medicine
  • Indiana Univ Hosp
  • Louisiana State Univ School of Medicine
  • Tulane Univ School of Medicine
  • Johns Hopkins Hosp
  • Harvard (Massachusetts Gen Hosp)
  • Beth Israel Deaconess - West Campus
  • Jack Weiler Hosp / Bronx Municipal Hosp
  • Montefiore Med Ctr / Bronx Municipal Hosp
  • North Central Bronx Hosp / Bronx Municipal Hosp
  • Bronx Veterans Administration / Mount Sinai Hosp
  • SUNY / Erie County Med Ctr at Buffalo
  • City Hosp Ctr at Elmhurst / Mount Sinai Hosp
  • Beth Israel Med Ctr / Peter Krueger Clinic
  • Bellevue Hosp / New York Univ Med Ctr
  • Cornell Univ Med Ctr
  • Mem Sloan - Kettering Cancer Ctr
  • Saint Luke's - Roosevelt Hosp Ctr
  • Mount Sinai Med Ctr
  • Univ of Rochester Medical Center
  • SUNY - Stony Brook
  • Univ of North Carolina
  • Duke Univ Med Ctr
  • Holmes Hosp / Univ of Cincinnati Med Ctr
  • Univ Hosp of Cleveland / Case Western Reserve Univ
  • Ohio State Univ Hosp Clinic
  • Julio Arroyo

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
March 11, 2011
Sponsor
Pfizer
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00001017
Brief Title
Comparison of Fluconazole and Amphotericin B in the Treatment of Brain Infections in Patients With AIDS
Official Title
Comparison of Fluconazole (UK-49,858) and Amphotericin B for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
September 2002
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
July 1991 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Pfizer
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningitis, Cryptococcal, HIV Infections
Keywords
AIDS-Related Opportunistic Infections, Meningitis, Injections, Intravenous, Cryptococcosis, Fluconazole, Administration, Oral, Acquired Immunodeficiency Syndrome, Amphotericin B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Enrollment
330 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Fluconazole
Intervention Type
Drug
Intervention Name(s)
Amphotericin B

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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). 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. Exclusion Criteria 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Armstrong D
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Dismukes W
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Powderly W
Official's Role
Study Chair
Facility Information:
Facility Name
UCLA CARE Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Univ of Miami School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
331361013
Country
United States
Facility Name
Indiana Univ Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Louisiana State Univ School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane Univ School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Johns Hopkins Hosp
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Harvard (Massachusetts Gen Hosp)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess - West Campus
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Jack Weiler Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10465
Country
United States
Facility Name
Montefiore Med Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
North Central Bronx Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Bronx Veterans Administration / Mount Sinai Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10468
Country
United States
Facility Name
SUNY / Erie County Med Ctr at Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
City
Elmhurst
State/Province
New York
ZIP/Postal Code
11373
Country
United States
Facility Name
Beth Israel Med Ctr / Peter Krueger Clinic
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Bellevue Hosp / New York Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cornell Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mem Sloan - Kettering Cancer Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Saint Luke's - Roosevelt Hosp Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
Facility Name
Mount Sinai Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Univ of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
SUNY - Stony Brook
City
Stony Brook
State/Province
New York
ZIP/Postal Code
117948153
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Duke Univ Med Ctr
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Holmes Hosp / Univ of Cincinnati Med Ctr
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
452670405
Country
United States
Facility Name
Univ Hosp of Cleveland / Case Western Reserve Univ
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Ohio State Univ Hosp Clinic
City
Columbus
State/Province
Ohio
ZIP/Postal Code
432101228
Country
United States
Facility Name
Julio Arroyo
City
West Columbia
State/Province
South Carolina
ZIP/Postal Code
29169
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
1727236
Citation
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.
Results Reference
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PubMed Identifier
1538722
Citation
Powderly 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.
Results Reference
background
PubMed Identifier
8075272
Citation
Powderly 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.
Results Reference
background
PubMed Identifier
1672443
Citation
McKinney 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.
Results Reference
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Comparison of Fluconazole and Amphotericin B in the Treatment of Brain Infections in Patients With AIDS

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