High dose amphotericin B with flucytosine, and amphotericin B plus high dose fluconazole for treatment of cryptococcal meningitis in human immunodeficiency (HIV)-infected patients

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN68133435
• Date of registration: 08/02/2006
• Prospective Registration: No
• Primary sponsor: St. George's Medical School (UK)
• Public title: High dose amphotericin B with flucytosine, and amphotericin B plus high dose fluconazole for treatment of cryptococcal meningitis in human immunodeficiency (HIV)-infected patients
• Scientific title: Early fungicidal activity of high dose amphotericin B combined with flucytosine, liposomal amphotericin B with flucytosine, amphotericin B and high dose fluconazole compared with standard amphotericin B and flucytosine for the initial treatment of human immunodeficiency virus associated cryptococcal meningitis
• Date of first enrolment: 01/06/2005
• Target sample size: 150
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN68133435
• Study type: Interventional
• Study design: Randomised controlled trial (Treatment)

Countries of recruitment

South Africa, Thailand

Contacts

• Name: Thomas Harrison

Key inclusion & exclusion criteria

Inclusion criteria: 1. 18 years old or more, either sex
2. Human immunodeficiency virus (HIV) seropositive
3. First episode of cryptococcal meningitis on basis of positive cerebrospinal fluid (CSF) India ink or CSF cryptococcal antigen
Exclusion criteria: 1. Liver function test - alanine aminotransferase (ALT) formerly known as serum glutamate pyruvate transaminase (SGPT) greater than five times upper limit of normal
2. Absolute neutrophil count less than 500 x 10^6/l
3. Platelets less than 50,000 x 10^6/l^3
4. Creatinine greater than 2.5 mg/dl^4
5. Pregnant or lactating women
6. Previous serious reaction to any of the study drugs
7. Currently taking systemic antifungal therapy

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Cryptococcal meningitis
Infections and Infestations
Cryptococcal meningitis

Intervention(s)

Step 1: high dose amphotericin B (1 mg/kg/day) plus flucytosine versus standard dose amphotericin B (0.7 mg/kg/day) plus flucytosine, for initial therapy.
Substudy step 1: high dose liposomal amphotericin B (10 mg/kg/day) plus flucytosine will be compared to high dose amphotericin B (1 mg/kg/day) plus flucytosine.

Step 2: the optimal dose of amphotericin (from the first step) will be combined with 800 mg/day of fluconazole, or 1200 mg/day of fluconazole compared with the standard regimen of amphotericin B plus flucytosine.

Primary Outcome(s)

Early fungicidal activity (EFA) of alternative regimens based on serial quantitative CSF cultures over the first two weeks of therapy.

Secondary Outcome(s)

1. Clinical and laboratory side effects
2. Mortality and morbidity at ten weeks

Secondary ID(s)

N/A

Source(s) of Monetary Support

British Infection Society (UK), Trustees of St. George?s Hospital, University of London (UK), The Wellcome Trust (UK) (grant ref: 052199), Medical Research Council (MRC) (UK) (grant ref: G0501476)