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

HIV Infections Clinical Trial

Official title:

Comparison of Fluconazole (UK-49,858) and Amphotericin B for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001017
• Other study ID #: ACTG 026
• Secondary ID: 056-158FDA 12E
• Status: Completed
• Phase: Phase 3
• First received: November 2, 1999
• Last updated: March 11, 2011

Study information

• Verified date: September 2002
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. primary completion date: July 1991
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes
• Infection
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• Fluconazole

• Amphotericin B

Locations

Country	Name	City	State
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Beth Israel Deaconess - West Campus	Boston	Massachusetts
United States	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts
United States	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York
United States	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York
United States	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio
United States	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	City Hosp Ctr at Elmhurst / Mount Sinai Hosp	Elmhurst	New York
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	UCLA CARE Ctr	Los Angeles	California
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Louisiana State Univ School of Medicine	New Orleans	Louisiana
United States	Tulane Univ School of Medicine	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr / Peter Krueger Clinic	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Mem Sloan - Kettering Cancer Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Saint Luke's - Roosevelt Hosp Ctr	New York	New York
United States	Univ of Rochester Medical Center	Rochester	New York
United States	SUNY - Stony Brook	Stony Brook	New York
United States	Julio Arroyo	West Columbia	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

External Links

•   Click here for more information about Amphotericin B
•   Click here for more information about Fluconazole