Condition category
Infections and Infestations
Date applied
25/01/2007
Date assigned
20/03/2007
Last edited
23/10/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Stephen Gillespie

ORCID ID

Contact details

Centre for Medical Microbiology
Royal Free and University College Medical School
Hampstead Campus
Rowland Hill Street
London
NW3 2PF
United Kingdom

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 measures

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

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

http://www.ucl.ac.uk

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

Results - basic reporting

See https://clinicaltrials.gov/ct2/show/results/NCT00864383

Publication summary

Publication citations

Additional files

Editorial Notes