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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. completion date
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


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

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