Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
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
Acronym
Study hypothesis
Higher doses of amphotericin B and of fluconazole are associated with more rapid clearance of infection.
Ethics approval
Ethical approval was obtained from:
1. REC Faculty of Health Sciences, University of Cape Town on 05/04/2004
2. Wandsworth LREC, London on 03/05/2005
3. Ethical Review Committee, Ministry of Public Health, Thailand on 02/09/2005
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Cryptococcal meningitis
Intervention
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.
Intervention type
Drug
Phase
Not Applicable
Drug names
High dose amphotericin B, flucytosine, amphotericin B, high dose fluconazole, flucytosine
Primary outcome measure
Early fungicidal activity (EFA) of alternative regimens based on serial quantitative CSF cultures over the first two weeks of therapy.
Secondary outcome measures
1. Clinical and laboratory side effects
2. Mortality and morbidity at ten weeks
Overall trial start date
01/06/2005
Overall trial end date
01/06/2007
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
150
Participant 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
Recruitment start date
01/06/2005
Recruitment end date
01/06/2007
Locations
Countries of recruitment
South Africa, Thailand
Trial participating centre
Department of Infectious Diseases
London
SW17 ORE
United Kingdom
Sponsor information
Organisation
St. George's Medical School (UK)
Sponsor details
Cranmer Terrace
London
SW17 ORE
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
British Infection Society (UK)
Alternative name(s)
BIS
Funding Body Type
private sector organisation
Funding Body Subtype
Associations and societies (private and public)
Location
United Kingdom
Funder name
Trustees of St. Georges Hospital, University of London (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Wellcome Trust (UK) (grant ref: 052199)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Medical Research Council (MRC) (UK) (grant ref: G0501476)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18505387
Publication citations
-
Results
Bicanic T, Wood R, Meintjes G, Rebe K, Brouwer A, Loyse A, Bekker LG, Jaffar S, Harrison T, High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial., Clin. Infect. Dis., 2008, 47, 1, 123-130, doi: 10.1086/588792.