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 |
| Protocol serial number | N/A |
| Sponsor | St. George's Medical School (UK) |
| Funders | British Infection Society (UK), Trustees of St. Georges Hospital, University of London (UK), The Wellcome Trust (UK) (grant ref: 052199), Medical Research Council (MRC) (UK) (grant ref: G0501476) |
- 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
Scientific
Department of Infectious Diseases
St. George's Medical School
Cranmer Terrace
London
SW17 ORE
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| 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 |
| Study objectives | Higher 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) studied | 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 / device / biological / vaccine name(s) | High dose amphotericin B, flucytosine, amphotericin B, high dose fluconazole, flucytosine |
| Primary outcome measure(s) |
Early fungicidal activity (EFA) of alternative regimens based on serial quantitative CSF cultures over the first two weeks of therapy. |
| Key secondary outcome measure(s) |
1. Clinical and laboratory side effects |
| Completion date | 01/06/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 150 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/06/2005 |
| Date of final enrolment | 01/06/2007 |
Locations
Countries of recruitment
- United Kingdom
- South Africa
- Thailand
Study participating centre
Department of Infectious Diseases
London
SW17 ORE
United Kingdom
SW17 ORE
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not 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 |
