Contact information
Type
Scientific
Primary contact
Dr Jeremy Farrar
ORCID ID
Contact details
Hospital for Tropical Diseases
The Hospital for Tropical Diseases
Oxford University Clinical Research
190 Ben Ham Tu
Ho Chi Minh City
5
Viet Nam
+84 88362225
jfarrar@oucru.org
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
061330
Study information
Scientific title
A randomised controlled trial of combination anti-fungal therapy in cryptococcal meningitis
Acronym
BK Study
Study hypothesis
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
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.
Study design
Open label randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
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 names
Fluconazole, amphotericin and flucytosine
Primary outcome measures
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 trial start date
22/04/2004
Overall trial end date
01/12/2009
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
300 (237 as of March 2009)
Participant exclusion criteria
1. Pregnancy
2. Renal or liver failure
3. Active TB
4. Aged less than 15 years old
Recruitment start date
22/04/2004
Recruitment end date
01/12/2009
Locations
Countries of recruitment
Viet Nam
Trial participating centre
Hospital for Tropical Diseases
Ho Chi Minh City
5
Viet Nam
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
The Wellcome Trust (UK) (grant ref: 061330)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23550668
Publication citations
-
Results
Day JN, Chau TT, Wolbers M, Mai PP, Dung NT, Mai NH, Phu NH, Nghia HD, Phong ND, Thai CQ, Thai le H, Chuong LV, Sinh DX, Duong VA, Hoang TN, Diep PT, Campbell JI, Sieu TP, Baker SG, Chau NV, Hien TT, Lalloo DG, Farrar JJ, Combination antifungal therapy for cryptococcal meningitis., N. Engl. J. Med., 2013, 368, 14, 1291-1302, doi: 10.1056/NEJMoa1110404.