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

ISRCTN ISRCTN07062956
DOI https://doi.org/10.1186/ISRCTN07062956
Secondary identifying numbers 061330
Submission date
22/07/2005
Registration date
22/07/2005
Last edited
06/02/2015
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 Guy Thwaites
Scientific

Oxford University Clinical Research Unit
The Hospital for Tropical Diseases
190 Ben Ham Tu
Ho Chi Minh City
5
Viet Nam

Phone +84 (0)8 9237954
Email guy.thwaites@btinternet.com

Study information

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific titleA randomised comparison of ciprofloxacin, levofloxacin and gatifloxacin for the treatment of adults with tuberculous meningitis
Study acronymBN study
Study objectivesFluoroquinolones 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(s)Not provided at time of registration
Health condition(s) or problem(s) studiedTuberculous meningitis
InterventionAdults 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Conventional four drug anti-tuberculosis chemotherapy (comprising of isoniazid, rifampicin, pyrazinamide and ethambutol), ciprofloxcin, levofloxacin and gatifloxacin.
Primary outcome measure1. 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 measuresNo secondary outcome measures
Overall study start date01/04/2003
Completion date01/02/2005

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participantsTo be added
Key inclusion criteria1. Aged over 14 years
2. Clinical diagnosis of TBM
Key exclusion criteria1. 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
Date of first enrolment01/04/2003
Date of final enrolment01/09/2004

Locations

Countries of recruitment

  • Viet Nam

Study participating centre

Oxford University Clinical Research Unit
Ho Chi Minh City
5
Viet Nam

Sponsor information

University of Oxford (UK)
University/education

University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom

Website http://www.ox.ac.uk
ROR logo "ROR" https://ror.org/052gg0110

Funders

Funder type

Charity

Wellcome Trust
Private sector organisation / International organizations
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/07/2011 Yes No