Tuberculosis Infections and Infestations Tuberculosis
Conditions
Interventions
Regimen one - control regimen:
Eight weeks of chemotherapy with ethambutol, isoniazid, rifampicin and pyrazinamide plus the moxifloxacin placebo, followed by nine weeks of isoniazid an
Sponsors
University College London (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Kenya, South Africa, Tanzania, Zambia
Outcome results
None listed