NCT00864383 REMoxTB.

Trial name or title	Controlled comparison of two moxifloxacin containing treatment shortening regimens in pulmonary TB CTRI/2011/05/001745 REMoxTB version 1.3
Methods	A randomized placebo controlled double blind trial comparing two treatment shortening regimens with the standard regimen (two months ethambutol, isoniazid, rifampicin, and pyrazinamide followed by four months isoniazid and rifampicin) namely 1) two months moxifloxacin, isoniazid, rifampicin, and pyrazinamide followed by two months moxifloxacin, isoniazid, and rifampicin and 2) two months ethambutol, moxifloxacin, rifampicin, and pyrazinamide followed by two months moxifloxacin and rifampicin for the treatment of adults with pulmonary TB ‐ REMoxTB. Randomized, parallel group, placebo controlled trial. Method of generating randomization sequence: random number table. Method of allocation concealment: pre‐numbered or coded identical containers. Blinding and masking: participant, investigator, outcome assessor, and data‐entry operator blinded.
Participants	Target sample size: 1800 Inclusion criteria: signed written consent or witnessed oral consent in the case of illiteracy, before undertaking any trial related activity; two sputum specimens positive for tubercle bacilli on direct smear microscopy at the local laboratory and confirmed at the study laboratory on a sample taken at screening; aged 18 years or over; no previous anti‐TB chemotherapy; 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; agreement to participate in the study and to give a sample of blood for HIV testing (see appendices 1 & 2); pre‐menopausal women must be using a barrier form of contraception or be surgically sterilized or have an IUCD in place; laboratory parameters performed up to 14 days before enrolment (Serum aspartate transaminase (AST) activity less than 3 times the upper limit of normal. Serum total bilirubin level less than 2.5 times upper limit of normal. Creatinine clearance (CrCl) level greater than 30 mLs/min. Haemoglobin level of at least 7.0 g/dL. Platelet count of at least 50x109cells/L. Serum potassium greater than 3.5 mmol/L); negative pregnancy test (women of childbearing potential). Exclusion criteria: unable to take oral medication; previously enrolled in this study; received any investigational drug in the past 3 months; received an antibiotic active against M. tuberculosis in the last 14 days (fluoroquinolones, macrolides, standard anti‐TB drugs); any condition that may prove fatal during the first two months of the study period; TB meningitis or other forms of severe TB with high risk of a poor outcome; pre‐existing non‐TB 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; pregnant or breast feeding; suffering from a condition likely to lead to uncooperative behaviour e.g. psychiatric illness or alcoholism; contraindications to any medications in the study regimens; 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); known allergy to any fluoroquinolone antibiotic or history of tendinopathy associated with quinolones; patients already receiving antiretroviral therapy; patients whose initial isolate is shown to be MDR‐TB; weight less than 35 kg; HIV infection with CD4 count less than 250 cells/µL; end stage liver failure (class Child‐Pugh C).
Interventions	Intervention 1: moxifloxacin in combination with ethambutol, pyrazinamide, and rifampicin: moxifloxacin, ethambutol, rifampicin, pyrazinamide for 2 months and moxifloxacin, rifampicin, and isoniazid placebo for 2 months and then isoniazid and rifampicin placebo for 2 months. Dose depend upon weight of the patient. Intervention 2: moxifloxacin in combination with isoniazid, pyrazinamide, and rifampicin: moxifloxacin, isoniazid, rifampicin, pyrazinamide for 2 months and moxifloxacin, isoniazid, and rifampicin for 2 months. Isoniazid and rifampicin placebo for 2 months. Dose depend upon weight of the patient. Control intervention 1: standard anti‐TB treatment: rifampicin, isoniazid, ethambutol, pyrazinamide for 2 months. Rifampicin and isoniazid and placebo for 4 months. Dose depend upon the weight of the patient.
Outcomes	Primary: 1. Efficacy: combined failure of bacteriological cure and relapse within one year of completion of therapy as defined by culture using solid media. 2. Safety: both comparisons: proportion of patients with grade 3 or 4 adverse events.Timepoint: 1.5 years Secondary: Efficacy: 1. Combined failure of bacteriological cure and relapse within one year of completion of therapy as defined by culture using liquid media. The following endpoints will be measured separately using both solid and liquid media. 2. Sensitivity analyses assuming all losses to follow‐up and non‐tuberculous deaths have an unfavourable outcome. 3. Sensitivity analyses assuming all losses to follow‐up and non‐tuberculous deaths have a favourable outcome. 4. Proportion of patients who are culture negative at eight weeks. 5. Time to first culture negative sputum sample. 6. Speed of decline of sputum viable count. Timepoint: 1.5 years.
Starting date	January 2008
Contact information	Stephen H Gillespie Tel: +44 (0) 20 7794 0500 ext.: 33539 s.gillespie@medsch.ucl.ac.uk Kapil Arora 579, Devli East Sainik Farms 110062New Delhi, DELHIIndia 011‐24502551 Kapil. Arora@apothecaries.net
Notes	Recruiting locations: Kenya, Centre for Respiratory Disease Research at KEMRI Nairobi; South Africa, Unit for Clinical & Biomedical TB Research, MRC Durban, South Africa, Tiervlei Trial Center and University of Stellenbosch, Cape Town, South Africa, Centre for TB Research and Innovation, UCT Lung Institute, Cape Town; Tanzania, Kilimanjaro Christian Medical Centre, Moshi; Tanzania, NIMR Mbeya Medical Research Programme, Mbeya; Zambia, University Teaching Hospital, Lusaka; China, India, Mexico, South Africa, Thailand, Global Alliance for TB Drug Development, New York, USA Primary sponsor: Apothecaries Private Limited http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=2686