Combination anti-fungal therapy in cryptococcal meningitis
| ISRCTN | ISRCTN95123928 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN95123928 |
| Secondary identifying numbers | 061330 |
- Submission date
- 22/07/2005
- Registration date
- 22/07/2005
- Last edited
- 05/04/2013
- 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 Jeremy Farrar
Scientific
Scientific
Hospital for Tropical Diseases
The Hospital for Tropical Diseases
Oxford University Clinical Research
190 Ben Ham Tu
Ho Chi Minh City
5
Viet Nam
| Phone | +84 88362225 |
|---|---|
| jfarrar@oucru.org |
Study information
| Study design | Open label randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | A randomised controlled trial of combination anti-fungal therapy in cryptococcal meningitis |
| Study acronym | BK Study |
| Study objectives | Cryptococcal meningitis is the second leading cause of death in Human Immunodeficiency Virus (HIV) patients worldwide after Tuberculosis (TB). The Hospital for Tropical Diseases has seen a dramatic increase in the number of cases of cryptococcal meningitis as the HIV epidemic has accelerated in Viet Nam. The mortality rate is high, even with treatment according to international guidelines. Optimum treatment for cryptococcal meningitis is not determined. Combination treatment with amphotericin and flucytosine has shown no clinical benefit when compared with amphotericin alone, yet this combination of potentially toxic drugs has become the standard of care, recommended in US and European guidelines. The azole drugs, with their ease of administration and good safety profile, have not been investigated in combination with amphotericin in the treatment of cryptococcal meningitis. The trial will determine whether amphotericin combined with high dose fluconazole is superior to amphotericin alone or amphotericin combined with flucytosine, using clinical endpoints. As of 18/03/2009 the anticipated trial dates of this record have been updated; the intial trial dates at the time of registration were: Initial anticipated start date: 01/04/2004 Initial anticipated end date: 01/01/2006 |
| Ethics approval(s) | The ethical review board of the Hospital for Tropical Diseases, Ho Chi Minh City, and Liverpool School of Tropical Medicine, UK gave approval prior to participant recruitment. |
| Health condition(s) or problem(s) studied | Cryptococcal meningitis |
| Intervention | Treatment Group 1: Induction Treatment: Amphotericin 1 mg/kg/day for 4 weeks Consolidation Treatment: Fluconazole 400 mg/day for 6 weeks Secondary Prophylaxis: Fluconazole 200 mg/day Treatment Group 2: Induction Treatment: Amphotericin 1 mg/kg/day plus flucytosine 100 mg/kg/day for 2 weeks Consolidation Treatment: Fluconazole 400 mg/day for 8 weeks Secondary Prophylaxis: Fluconazole 200 mg/day Treatment Group 3: Induction Treatment: Amphotericin 1 mg/kg/day plus Fluconazole 800 mg/day for 2 weeks Consolidation Treatment: Fluconazole 400 mg/day for 8 weeks Secondary Prophylaxis: Fluconazole 200 mg/day |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Fluconazole, amphotericin and flucytosine |
| Primary outcome measure | Mortality at 2 and 10 weeks |
| Secondary outcome measures | Amended as of 19/03/2009: 1. Rates of disability at 10 weeks 2. Rates of clearance of yeasts from CSF at 6 months 3. Changes in immune parameters at 6 months 4. Combined death and disability at 6 months 5. Death at 6 months Initial information at the time of registration: 1. Duration of ventilation 2. Duration of supplemental oxygen 3. Duration of hospitalisation 4. Viral load in clinical specimens 5. Cytokine levels 6. Adverse effects |
| Overall study start date | 22/04/2004 |
| Completion date | 01/12/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 300 (237 as of March 2009) |
| Key inclusion criteria | 1. Patients aged 15 years and older 2. HIV positive 3. Cryptococcal meningitis defined by a clinical syndrome consistent with cryptococcal meningitis and one or more of: positive Cerebrospinal Fluid (CSF) culture, positive cryptococcal antigen in CSF, positive CSF india ink test |
| Key exclusion criteria | 1. Pregnancy 2. Renal or liver failure 3. Active TB 4. Aged less than 15 years old |
| Date of first enrolment | 22/04/2004 |
| Date of final enrolment | 01/12/2009 |
Locations
Countries of recruitment
- Viet Nam
Study participating centre
Hospital for Tropical Diseases
Ho Chi Minh City
5
Viet Nam
5
Viet Nam
Sponsor information
University of Oxford (UK)
University/education
University/education
University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
| Website | http://www.ox.ac.uk |
|---|---|
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
The Wellcome Trust (UK) (grant ref: 061330)
No information available
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 | 04/04/2013 | Yes | No |
