Condition category
Infections and Infestations
Date applied
22/07/2005
Date assigned
22/07/2005
Last edited
06/02/2015
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 Guy Thwaites

ORCID ID

Contact details

Oxford University Clinical Research Unit
The Hospital for Tropical Diseases
190 Ben Ham Tu
Ho Chi Minh City
5
Viet Nam
+84 (0)8 9237954
guy.thwaites@btinternet.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

061330

Study information

Scientific title

A randomised comparison of ciprofloxacin, levofloxacin and gatifloxacin for the treatment of adults with tuberculous meningitis

Acronym

BN study

Study hypothesis

Fluoroquinolones are bactericidal for Mycobacterium tuberculosis and are recommended by the World Health Organisation (WHO) for the treatment of multi-drug resistant pulmonary tuberculosis. Reports of their use in Tuberculous Meningitis (TBM) are restricted to case reports, and there are no controlled trials to clarify their role in management. In particular, data regarding Cerebrospinal Fluid (CSF) penetration and pharmacokinetics are scant, and it is uncertain which of the fluoroquinolones represents the best drug for treating TBM.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Tuberculous meningitis

Intervention

Adults entering the study will be randomised to one of four treatment arms:
1. Conventional four drug Anti-Tuberculosis Chemotherapy (ATC) (comprising of isoniazid, rifampicin, pyrazinamide and ethambutol)
2. Conventional four drug ATC plus ciprofloxcin
3. Conventional four drug ATC plus levofloxacin
4. Conventional four drug ATC plus gatifloxacin.

The trial will be open-label. Sparse pharmacokinetic data will be generated from routine serial sampling of CSF/plasma performed upon each patient for the purposes of assessing response to treatment. Paired blood and CSF samples (for drug measurement and killing curves) will be taken at diagnosis, day two, day seven, day 30, and day 60. The precise timing of the Lumbar Puncture (LP), in relation to drug administration, will be randomised. Likewise, the timing of two further specimens of plasma (taken either side of the LP) will also be randomised.

Intervention type

Drug

Phase

Not Applicable

Drug names

Conventional four drug anti-tuberculosis chemotherapy (comprising of isoniazid, rifampicin, pyrazinamide and ethambutol), ciprofloxcin, levofloxacin and gatifloxacin.

Primary outcome measures

1. Clinical methods: the following will be used as markers of clinical response:
a. fever clearance, coma clearance, date of discharge, death at two months, disability or death at nine months
b. CSF pressure, lactate, white cell count, protein and glucose
2. Microbiological methods: we will attempt to demonstrate microbiological activity by two methods:
a. time to CSF sterility - serial lumbar punctures will allow us to assess the time taken to kill TBM in the CSF. 60% of adults with TBM isolated from the CSF before treatment have a sterile CSF after 48 hours of treatment, and 5% (often with resistant organisms) have TBM cultured from the CSF after 30 days of treatment (unpublished data from HTD). We aim to compare time to CSF sterility in the four treatment arms
b. time to negative CSF amplified TBM direct test (Mycobacterium Tuberculosis Direct [MTD] test: Gen-probe, California). Using the same principles described above, we will compare time to negative MTD in the four treatment arms

Secondary outcome measures

No secondary outcome measures

Overall trial start date

01/04/2003

Overall trial end date

01/02/2005

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged over 14 years
2. Clinical diagnosis of TBM

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

To be added

Participant exclusion criteria

1. Patients who are less than 15 years old
2. Patients who are pregnant or breast feeding
3. Patients in whom the physician believes fluoroquinolones are contraindicated e.g. previous adverse reaction
4. The consent of either the patient or their relatives is not obtained

Recruitment start date

01/04/2003

Recruitment end date

01/09/2004

Locations

Countries of recruitment

Viet Nam

Trial participating centre

Oxford University Clinical Research Unit
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

Wellcome Trust

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

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

2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21502621

Publication citations

  1. Results

    Thwaites GE, Bhavnani SM, Chau TT, Hammel JP, Török ME, Van Wart SA, Mai PP, Reynolds DK, Caws M, Dung NT, Hien TT, Kulawy R, Farrar J, Ambrose PG, Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis., Antimicrob. Agents Chemother., 2011, 55, 7, 3244-3253, doi: 10.1128/AAC.00064-11.

Additional files

Editorial Notes