Plain English Summary

Not provided at time of registration

Trial website

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

http://www.ox.ac.uk

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

  1. 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.

Editorial Notes