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

ISRCTN ISRCTN68133435
DOI https://doi.org/10.1186/ISRCTN68133435
Secondary identifying numbers N/A
Submission date
30/09/2005
Registration date
08/02/2006
Last edited
21/03/2013
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Thomas Harrison
Scientific

Department of Infectious Diseases
St. George's Medical School
Cranmer Terrace
London
SW17 ORE
United Kingdom

Study information

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific titleEarly 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
Study objectivesHigher doses of amphotericin B and of fluconazole are associated with more rapid clearance of infection.
Ethics approval(s)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
Health condition(s) or problem(s) studiedCryptococcal meningitis
InterventionStep 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)High dose amphotericin B, flucytosine, amphotericin B, high dose fluconazole, flucytosine
Primary outcome measureEarly fungicidal activity (EFA) of alternative regimens based on serial quantitative CSF cultures over the first two weeks of therapy.
Secondary outcome measures1. Clinical and laboratory side effects
2. Mortality and morbidity at ten weeks
Overall study start date01/06/2005
Completion date01/06/2007

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants150
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment01/06/2005
Date of final enrolment01/06/2007

Locations

Countries of recruitment

  • South Africa
  • Thailand
  • United Kingdom

Study participating centre

Department of Infectious Diseases
London
SW17 ORE
United Kingdom

Sponsor information

St. George's Medical School (UK)
University/education

Cranmer Terrace
London
SW17 ORE
United Kingdom

Website http://www.sgul.ac.uk/
ROR logo "ROR" https://ror.org/040f08y74

Funders

Funder type

University/education

British Infection Society (UK)
Private sector organisation / Associations and societies (private and public)
Alternative name(s)
BIS
Location
United Kingdom
Trustees of St. George’s Hospital, University of London (UK)

No information available

The Wellcome Trust (UK) (grant ref: 052199)

No information available

Medical Research Council (MRC) (UK) (grant ref: G0501476)
Government organisation / National government
Alternative name(s)
Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/07/2008 Yes No