Condition category
Infections and Infestations
Date applied
30/09/2005
Date assigned
08/02/2006
Last edited
21/03/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Thomas Harrison

ORCID ID

Contact details

Department of Infectious Diseases
St. George's Medical School
Cranmer Terrace
London
SW17 ORE
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Early fungicidal activity of high dose amphotericin B combined with flucytosine, liposomal amphotericin B with flucytosine, amphotericin B and high dose fluconazole compared with standard amphotericin B and flucytosine for the initial treatment of human immunodeficiency virus associated cryptococcal meningitis

Acronym

Study hypothesis

Higher doses of amphotericin B and of fluconazole are associated with more rapid clearance of infection.

Ethics approval

Ethical approval was obtained from:
1. REC Faculty of Health Sciences, University of Cape Town on 05/04/2004
2. Wandsworth LREC, London on 03/05/2005
3. Ethical Review Committee, Ministry of Public Health, Thailand on 02/09/2005

Study design

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

Step 1: high dose amphotericin B (1 mg/kg/day) plus flucytosine versus standard dose amphotericin B (0.7 mg/kg/day) plus flucytosine, for initial therapy.
Substudy step 1: high dose liposomal amphotericin B (10 mg/kg/day) plus flucytosine will be compared to high dose amphotericin B (1 mg/kg/day) plus flucytosine.

Step 2: the optimal dose of amphotericin (from the first step) will be combined with 800 mg/day of fluconazole, or 1200 mg/day of fluconazole compared with the standard regimen of amphotericin B plus flucytosine.

Intervention type

Drug

Phase

Not Applicable

Drug names

High dose amphotericin B, flucytosine, amphotericin B, high dose fluconazole, flucytosine

Primary outcome measures

Early fungicidal activity (EFA) of alternative regimens based on serial quantitative CSF cultures over the first two weeks of therapy.

Secondary outcome measures

1. Clinical and laboratory side effects
2. Mortality and morbidity at ten weeks

Overall trial start date

01/06/2005

Overall trial end date

01/06/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. 18 years old or more, either sex
2. Human immunodeficiency virus (HIV) seropositive
3. First episode of cryptococcal meningitis on basis of positive cerebrospinal fluid (CSF) India ink or CSF cryptococcal antigen

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

150

Participant exclusion criteria

1. Liver function test - alanine aminotransferase (ALT) formerly known as serum glutamate pyruvate transaminase (SGPT) greater than five times upper limit of normal
2. Absolute neutrophil count less than 500 x 10^6/l
3. Platelets less than 50,000 x 10^6/l^3
4. Creatinine greater than 2.5 mg/dl^4
5. Pregnant or lactating women
6. Previous serious reaction to any of the study drugs
7. Currently taking systemic antifungal therapy

Recruitment start date

01/06/2005

Recruitment end date

01/06/2007

Locations

Countries of recruitment

South Africa, Thailand

Trial participating centre

Department of Infectious Diseases
London
SW17 ORE
United Kingdom

Sponsor information

Organisation

St. George's Medical School (UK)

Sponsor details

Cranmer Terrace
London
SW17 ORE
United Kingdom

Sponsor type

University/education

Website

http://www.sgul.ac.uk/

Funders

Funder type

University/education

Funder name

British Infection Society (UK)

Alternative name(s)

BIS

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Funder name

Trustees of St. George’s Hospital, University of London (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Wellcome Trust (UK) (grant ref: 052199)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Medical Research Council (MRC) (UK) (grant ref: G0501476)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

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

2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18505387

Publication citations

  1. Results

    Bicanic T, Wood R, Meintjes G, Rebe K, Brouwer A, Loyse A, Bekker LG, Jaffar S, Harrison T, High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial., Clin. Infect. Dis., 2008, 47, 1, 123-130, doi: 10.1086/588792.

Additional files

Editorial Notes