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

Study website

Contact information

Prof Stephen Gillespie
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 designMulticentre randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific titleControlled comparison of two moxifloxacin containing treatment shortening regimens in pulmonary tuberculosis
Study acronymREMoxTB
Study objectives1. 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) studiedTuberculosis
InterventionRegimen 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Moxifloxacin, isoniazid, rifampicin and pyrazinamide, ethambutol
Primary outcome measure1. 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 measuresEfficacy:
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 date01/06/2007
Completion date01/01/2011

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants1500
Key inclusion criteria1. 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 criteria1. 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 enrolment01/06/2007
Date of final enrolment01/01/2011

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

Sponsor information

University College London (UK)
University/education

Gower Street
London
WC1E 6BT
England
United Kingdom

Website http://www.ucl.ac.uk
ROR logo "ROR" https://ror.org/02jx3x895

Funders

Funder type

Industry

European and Developing Countries Clinical Trials Partnership (EDCTP) (The Netherlands)
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 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?
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.