Combination anti-fungal therapy in cryptococcal meningitis

ISRCTN	ISRCTN95123928
DOI	https://doi.org/10.1186/ISRCTN95123928
Protocol serial number	061330
Sponsor	University of Oxford (UK)
Funder	The Wellcome Trust (UK) (grant ref: 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

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
Email	jfarrar@oucru.org

Study information

Primary study design	Interventional
Study design	Open label randomised controlled trial
Secondary study design	Randomised controlled trial
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
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Fluconazole, amphotericin and flucytosine
Primary outcome measure(s)	Mortality at 2 and 10 weeks
Key secondary outcome measure(s)	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
Completion date	01/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	300
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

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	04/04/2013		Yes	No