Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00864383
Protocol/serial number
N/A
Study information
Scientific title
Controlled comparison of two moxifloxacin containing treatment shortening regimens in pulmonary tuberculosis
Acronym
REMoxTB
Study hypothesis
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
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.
Study design
Multicentre randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Not Applicable
Drug names
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 trial start date
01/06/2007
Overall trial end date
01/01/2011
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1500
Participant 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
Recruitment start date
01/06/2007
Recruitment end date
01/01/2011
Locations
Countries of recruitment
Kenya, South Africa, Tanzania, Zambia
Trial participating centre
Royal Free and University College Medical School
London
NW3 2PF
United Kingdom
Sponsor information
Organisation
University College London (UK)
Sponsor details
Gower Street
London
WC1E 6BT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
European and Developing Countries Clinical Trials Partnership (EDCTP) (The Netherlands)
Alternative name(s)
EDCTP
Funding Body Type
private sector organisation
Funding Body Subtype
international
Location
Netherlands
Funder name
TB Alliance (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Bayer HealthCare Pharmaceuticals (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sanofi-Aventis (France)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
Basic results (scientific)
See https://clinicaltrials.gov/ct2/show/results/NCT00864383
Publication list