Controlled comparison of two moxifloxacin containing treatment shortening regimens in pulmonary tuberculosis
| ISRCTN | ISRCTN85595810 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN85595810 |
| ClinicalTrials.gov number | NCT00864383 |
| Secondary identifying numbers | N/A |
- Submission date
- 25/01/2007
- Registration date
- 20/03/2007
- Last edited
- 10/04/2019
- 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
http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=29
Contact information
Prof Stephen Gillespie
Scientific
Scientific
Centre for Medical Microbiology
Royal Free and University College Medical School
Hampstead Campus
Rowland Hill Street
London
NW3 2PF
United Kingdom
Study information
| Study design | Multicentre randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | Controlled comparison of two moxifloxacin containing treatment shortening regimens in pulmonary tuberculosis |
| Study acronym | REMoxTB |
| Study objectives | 1. In treatment-naïve adults with active pulmonary Tuberculosis (TB) treated with eight weeks of moxifloxacin, isoniazid, rifampicin and pyrazinamide (i.e. a standard regimen where moxifloxacin is substituted for ethambutol), followed by nine weeks of moxifloxacin, isoniazid and rifampicin, followed by nine weeks of placebo, the proportion of patients who experience treatment failure or disease relapse in the twelve months following treatment completion will not be inferior to that observed in patients who are treated with a standard regimen (eight weeks of ethambutol, isoniazid, rifampicin and pyrazinamide followed by eighteen weeks of isoniazid plus rifampicin). 2. In treatment-naïve adults with active pulmonary TB treated with eight weeks of ethambutol, moxifloxacin, rifampicin and pyrazinamide (i.e. a standard regimen where moxifloxacin is substituted for isoniazid), followed by nine weeks of moxifloxacin and rifampicin followed by nine weeks of placebo, the proportion of patients who experience treatment failure or disease relapse in the twelve months following treatment completion will not be inferior to that observed in patients who are treated with a standard regimen (eight weeks of ethambutol, isoniazid, rifampicin and pyrazinamide followed by eighteen weeks of isoniazid plus rifampicin). |
| Ethics approval(s) | University College London (UCL) Research Ethics Committee, 05/04/2006, ref:0670/001. Each trial site will apply to the appropriate institutional research ethics committee, approval must be granted before recruitment commences at that site. |
| Health condition(s) or problem(s) studied | Tuberculosis |
| Intervention | Regimen one - control regimen: Eight weeks of chemotherapy with ethambutol, isoniazid, rifampicin and pyrazinamide plus the moxifloxacin placebo, followed by nine weeks of isoniazid and rifampicin plus the moxifloxacin placebo, followed by nine weeks of isoniazid and rifampicin only. Regimen two: Eight weeks of chemotherapy with moxifloxacin, isoniazid, rifampicin and pyrazinamide plus the ethambutol placebo, followed by nine weeks of moxifloxacin, isoniazid and rifampicin, followed by nine weeks of the isoniazid placebo and the rifampicin placebo. Regimen three: Eight weeks of chemotherapy with ethambutol, moxifloxacin, rifampicin and pyrazinamide plus the isoniazid placebo, followed by nine weeks of moxifloxacin and rifampicin plus the isoniazid placebo, followed by nine weeks of the isoniazid placebo and the rifampicin placebo. Dosages are dependent on the weight category of the patient, and will be provided as follows (all drugs are taken orally): 1. Moxifloxacin: 400 mg 2. Rifampicin: a. Less than or equal to 45 kg = 450 mg b. Greater than 45 kg = 600 mg 3. Isoniazid: 300 mg 4. Pyrazinamide: a. Less than 40 kg = 25 mg/kg rounded to nearest 500 mg b. 40 to 55 kg = 1000 mg c. Greater than 55 kg to 75 kg = 1500 mg d. Greater than 75 kg = 2000 mg 5. Ethambutol: a. Less than 40 kg = 15 mg/kg rounded to nearest 100 mg b. 40 to 55 kg = 800 mg c. Greater than 55 kg to 75 kg = 1200 mg d. Greater than 75 kg = 1600 mg |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Moxifloxacin, isoniazid, rifampicin and pyrazinamide, ethambutol |
| Primary outcome measure | 1. Efficacy : Combined failure of bacteriological cure and relapse within one year of completion of therapy 2. Safety : Proportion of patients with grade three or four Adverse Events (AEs) according to the World Health Organisation (WHO) grade |
| Secondary outcome measures | Efficacy: 1. Proportion of patients who are culture negative at eight weeks 2. Time to first culture negative sputum sample 3. Speed of decline of sputum viable count |
| Overall study start date | 01/06/2007 |
| Completion date | 01/01/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1500 |
| Key inclusion criteria | 1. Signed written consent or witnessed oral consent in the case of illiteracy, before undertaking any trial related activity 2. Two sputum specimens positive for tubercle bacilli on direct smear microscopy at the local laboratory 3. No previous anti-tuberculosis chemotherapy 4. Aged 18 years and over 5. A firm home address that is readily accessible for visiting and willingness to inform the study team of any change of address during the treatment and follow-up period 6. Agreement to participate in the study and to give a sample of blood for Human Immunodeficiency Virus (HIV) testing 7. Laboratory parameters performed up to 14 days before enrolment 8. Serum aspartate aminotransferase (AST) activity less than three times the Upper Limit of Normal (ULN) 9. Serum total bilirubin level less than 2.5 times ULN 10. Creatinine Clearance (CrCl) level greater than 30 mls/min 11. Haemoglobin level of at least 7.0 g/dL 12. Platelet count of at least 50 x 10^9 cells/L 13. Serum potassium greater than 3.5 mmol/L 14. Negative pregnancy test (women of childbearing potential) 15. Pre-menopausal women must be using a barrier form of contraception or be surgically sterilised or have an Intra-Uterine Contraceptive Device (IUCD) in place |
| Key exclusion criteria | 1. Unable to take oral medication 2. Previously enrolled in this study 3. Received any investigational drug in the past three months 4. Received an antibiotic active against M. tuberculosis in the last 14 days (fluoroquinolones, macrolides, standard anti-tuberculosis drugs) 5. Any condition that may prove fatal during the first two months of the study period 6. TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome 7. Pre-existing non-tuberculosis disease likely to prejudice the response to, or assessment of, treatment e.g. insulin-dependent diabetes, liver or kidney disease, blood disorders, peripheral neuritis, chronic diarrhoeal disease 8. Pregnant or breast feeding 9. Suffering from a condition likely to lead to uncooperative behaviour e.g. psychiatric illness or alcoholism 10. Contraindications to any medications in the study regimens 11. Known to have congenital or sporadic syndromes of QTc prolongation or receiving concomitant medication reported to increase the QTc interval (e.g. amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine) 12. End stage liver failure (class Child-Pugh C) 13. Uncorrected hypokalaemia 14. Weight less than 35 kg 15. Known allergy to any fluoroquinolone antibiotic or history of tendinopathy associated with quinolones 16. HIV infection with CD4 count less than 250 x 10^9/lit 17. Patients already receiving anti-retroviral therapy 18. Patients whose initial isolate is shown to be multiple drug resistant |
| Date of first enrolment | 01/06/2007 |
| Date of final enrolment | 01/01/2011 |
Locations
Countries of recruitment
- England
- Kenya
- South Africa
- Tanzania
- United Kingdom
- Zambia
Study participating centre
Royal Free and University College Medical School
London
NW3 2PF
United Kingdom
NW3 2PF
United Kingdom
Sponsor information
University College London (UK)
University/education
University/education
Gower Street
London
WC1E 6BT
England
United Kingdom
| Website | http://www.ucl.ac.uk |
|---|---|
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Industry
European and Developing Countries Clinical Trials Partnership (EDCTP) (The Netherlands)
Private sector organisation / International organizations
Private sector organisation / International organizations
- Alternative name(s)
- Le partenariat Europe-Pays en développement pour les essais cliniques, A Parceria entre a Europa e os Países em Desenvolvimento para a Realização de Ensaios Clínicos, The European & Developing Countries Clinical Trials Partnership, European and Developing Countries Clinical Trials, EDCTP
- Location
- Netherlands
TB Alliance (USA)
No information available
Bayer HealthCare Pharmaceuticals (USA)
No information available
Sanofi-Aventis (France)
No information available
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? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| Results article | results | 23/10/2014 | 10/04/2019 | Yes | No |
| Results article | results | 04/02/2016 | 10/04/2019 | Yes | No |
| Results article | results | 01/05/2018 | 10/04/2019 | Yes | No |
Editorial Notes
10/04/2019: Publication reference added.
