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
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 |
---|---|
guy.thwaites@btinternet.com |
Study information
Study design | Randomised controlled trial |
---|---|
Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Not specified |
Study type | Treatment |
Scientific title | A randomised comparison of ciprofloxacin, levofloxacin and gatifloxacin for the treatment of adults with tuberculous meningitis |
Study acronym | BN study |
Study objectives | 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(s) | Not provided at time of registration |
Health condition(s) or problem(s) studied | 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 |
Pharmaceutical study type(s) | |
Phase | Not 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 measure | 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 study start date | 01/04/2003 |
Completion date | 01/02/2005 |
Eligibility
Participant type(s) | Patient |
---|---|
Age group | Adult |
Sex | Both |
Target number of participants | To be added |
Key inclusion criteria | 1. Aged over 14 years 2. Clinical diagnosis of TBM |
Key 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 |
Date of first enrolment | 01/04/2003 |
Date of final enrolment | 01/09/2004 |
Locations
Countries of recruitment
- Viet Nam
Study participating centre
Oxford University Clinical Research Unit
Ho Chi Minh City
5
Viet Nam
5
Viet Nam
Sponsor information
University of Oxford (UK)
University/education
University/education
University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
Website | http://www.ox.ac.uk |
---|---|
https://ror.org/052gg0110 |
Funders
Funder type
Charity
Wellcome Trust
Private sector organisation / International organizations
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
Intention to publish date | |
---|---|
Individual participant data (IPD) Intention to share | No |
IPD sharing plan summary | Not provided at time of registration |
Publication and dissemination plan | Not 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 |