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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00001017
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 330
• Locations: 28
• Patients Per Site: 11.8

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Meningitis, Cryptococcal; HIV Infections	Drug: Fluconazole; Drug: Amphotericin B	Phase 3

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

• Study Type: Interventional
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official Title: Comparison of Fluconazole (UK-49,858) and Amphotericin B for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome
• Actual Primary Completion Date: Jul 1, 1991

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA CARE Ctr	Los Angeles	California	United States	90095
2	Univ of Miami School of Medicine	Miami	Florida	United States	331361013
3	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
4	Louisiana State Univ School of Medicine	New Orleans	Louisiana	United States	70112
5	Tulane Univ School of Medicine	New Orleans	Louisiana	United States	70112
6	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
7	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts	United States	02114
8	Beth Israel Deaconess - West Campus	Boston	Massachusetts	United States	02215
9	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York	United States	10465
10	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10467
11	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York	United States	10467
12	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York	United States	10468
13	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York	United States	14215
14	City Hosp Ctr at Elmhurst / Mount Sinai Hosp	Elmhurst	New York	United States	11373
15	Beth Israel Med Ctr / Peter Krueger Clinic	New York	New York	United States	10003
16	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
17	Cornell Univ Med Ctr	New York	New York	United States	10021
18	Mem Sloan - Kettering Cancer Ctr	New York	New York	United States	10021
19	Saint Luke's - Roosevelt Hosp Ctr	New York	New York	United States	10025
20	Mount Sinai Med Ctr	New York	New York	United States	10029
21	Univ of Rochester Medical Center	Rochester	New York	United States	14642
22	SUNY - Stony Brook	Stony Brook	New York	United States	117948153
23	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
24	Duke Univ Med Ctr	Durham	North Carolina	United States	27710
25	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio	United States	452670405
26	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio	United States	44106
27	Ohio State Univ Hosp Clinic	Columbus	Ohio	United States	432101228
28	Julio Arroyo	West Columbia	South Carolina	United States	29169

Sponsors and Collaborators

• Pfizer
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Armstrong D,
• Study Chair: Dismukes W,
• Study Chair: Powderly W,

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.

• ClinicalTrials.gov Identifier: NCT00001017
• Other Study ID Numbers: ACTG 026; 056-158; FDA 12E
• First Posted: Aug 31, 2001
• Last Update Posted: Mar 14, 2011
• Last Verified: Sep 1, 2002

• Keywords provided by , ,: AIDS-Related Opportunistic Infections; Meningitis; Injections, Intravenous; Cryptococcosis; Fluconazole; Administration, Oral; Acquired Immunodeficiency Syndrome; Amphotericin B
• Additional relevant MeSH terms: Infections; Acquired Immunodeficiency Syndrome; Meningitis, Cryptococcal; Meningitis; Fluconazole; Amphotericin B; Liposomal amphotericin B

Study Results

No Results Posted as of Mar 14, 2011