High dose fluconazole with or without flucytosine in the treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitiscryptococcal meningitis
| ISRCTN | ISRCTN02725351 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN02725351 |
| Secondary identifying numbers | MRC (UK) ref: 76201; 1.0 |
- Submission date
- 11/02/2008
- Registration date
- 20/03/2008
- Last edited
- 05/01/2010
- 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
Prof Thomas Harrison
Scientific
Scientific
Cranmer Terrace
London
SW17 ORE
United Kingdom
Study information
| Study design | Randomised open-labelled controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A randomised controlled clinical trial to evaluate high dose fluconazole with or without flucytosine in the treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitis |
| Study objectives | As of 27/02/2009 this record was updated to include the second phase Step 2 within this record. Ethics approval was extended to include this phase. All additions to this record regarding Step 2 can be found in the relevant field under the title Step 2. The titles for Step 2 are as follows: Step 2 public title: High dose fluconazole with short course amphotericin B, with or without flucytosine in the treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitis Step 2 scientific title: A randomised controlled clinical trial to evaluate high dose fluconazole with short course amphotericin B, with or without flucytosine in the treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitis Please also note that the anticipated start and end dates for Step 2 are as follows: Step 2 anticipated start date: 01/03/2009 Step 2 anticipated end date: 01/01/2010 At the time of registration, the initial trial dates reflected Step 1 of this trial, and therefore these have been amended to include the Step 2 dates as above; the initial end date (for Step 1) was 18/02/2009. Step 1 hypothesis: Addition of flucytosine to fluconazole will lead to more rapid sterilisation of cerebrospinal fluid (CSF) in cryptococcal meningitis. Step 2 hypotheses: 1. In the presence of a short course of amphotericin B, the addition of flucytosine to fluconazole (1200 mg/d) will lead to more rapid sterilisation of cerebrospinal fluid (CSF) in cryptococcal meningitis 2. A short course of amphotericin B will avoid toxicity observed in longer courses of amphotericin B. |
| Ethics approval(s) | 1. Malawi National Health Sciences Research Committee approved on the 8th November 2007 (Step 2 amendment: 17th February 2009) 2. Wandsworth LREC (covering St Georges University of London UK) approved on the 8th January 2008 (Step 2 amendment: 13th February 2009) 3. Institutional review board (IRB) University of North Carolina at Chapel Hill approved on the 29th November 2007 (Step 2 amendment pending as of 26/02/2009) |
| Health condition(s) or problem(s) studied | Cryptococcal meningitis/ HIV |
| Intervention | Step 1: 1. Fluconazole 1,200 mg/d for two weeks 2. Fluconazole 1,200 mg/d plus flucytosine 100 mg/kg/d for two weeks After two weeks all patients receive fluconazole 800 mg/d. Step 2: 1. Amphotericin B 1 mg/kg daily for 7 days plus fluconazole 1200 mg/d (started concurrently) for 2 weeks 2. Amphotericin B 1 mg/kg daily for 7 days, plus fluconazole 1200 mg/d, plus flycytosine 100 mg/kg/day (started concurrently) for 2 weeks After two weeks all patients receive fluconazole 800 mg/d. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Fluconazole, flucytosine |
| Primary outcome measure | Early fungicidal activity (rate of clearance of infection) of alternative regimens over the first two weeks of therapy. |
| Secondary outcome measures | 1. Clinical and laboratory side effects 2. Mortality at 2 and 10 weeks |
| Overall study start date | 18/02/2008 |
| Completion date | 01/01/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 80 |
| Key inclusion criteria | 1. Patients greater than 18 years, either sex 2. A first episode of cryptococcal meningitis |
| Key exclusion criteria | 1. Alanine aminotransferase (ALT) greater than five times the upper limit of normal 2. Pregnancy or lactation 3. Previous serious reaction to study drugs 4. Taking systemic anti-fungals 5. Polymorphonuclear leukocytes (PMNs) less than 500 x 10^6/L 6. Platelets less than 50,000 x 10^6/L 7. Concomitant medication that is contraindicated with any study drugs 8. Already on antiretroviral therapy (ART) STEP 2 additional criteria: 9. Initial creatinine greater than 2.5 mg/dl |
| Date of first enrolment | 18/02/2008 |
| Date of final enrolment | 01/01/2010 |
Locations
Countries of recruitment
- Malawi
- United Kingdom
Study participating centre
Cranmer Terrace
London
SW17 ORE
United Kingdom
SW17 ORE
United Kingdom
Sponsor information
St George's University of London (UK)
University/education
University/education
Cranmer Terrace
London
SW17 ORE
United Kingdom
| Website | http://www.sgul.ac.uk |
|---|---|
"ROR" |
https://ror.org/040f08y74 |
Funders
Funder type
Research council
Medical Research Council (UK) (grant ID: 76201)
Government organisation / National government
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 share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 | 01/02/2010 | Yes | No |
