Velayutham 2014.

Methods	Study design: randomized, open‐label, parallel‐group, 5‐arm, active‐controlled trial Study period: patient recruitment commenced in May 2007 (interim results of an ongoing trial) Recruitment sites: Chennai, Madurai Country where the trial was undertaken: India Length of follow‐up: 24 months after treatment completion
Participants	No. of participants randomized: 801 (of the 1650 anticipated) Combined intervention arms: 3 to 4 months moxifloxacin: N = 629 Control: 6 months ATT: N = 172 Age: < 35 years: moxifloxacin 52%; control 52% Gender: male: moxifloxacin 74%; control 77% Inclusion criteria: Adult patients, 18 years or older, with newly diagnosed sputum smear positive pulmonary tuberculosis Resident within a designated study area and permitted home visits. Exclusion criteria: Those with previous treatment for tuberculosis exceeding 30 days, weighing over 30 kg, pregnant or lactating women Those with concomitant diabetes mellitus, severe systemic hypertension, epilepsy, serious forms of extrapulmonary tuberculosis, or HIV infection Proportion with HIV seropositivity: nil (excluded) Proportion with cavitation: moxifloxacin 36%; control 41% Baseline drug resistance: isoniazid (moxifloxacin 7%; control 8%); ofloxacin (moxifloxacin 5%; control 7%); rifampicin, ethambutol, isoniazid, and ethambutol; isoniazid and ofloxacin (< 1% in both groups)
Interventions	Interventions: 3‐ and 4‐month moxifloxacin regimens: moxifloxacin added to standard ATT drugs N = 629 randomized; 13 exclusions; 616 (98%) evaluated of those randomized Rifampicin, isoniazid, pyrazinamide, ethambutol, and moxifloxacin daily for 3 months Rifampicin, isoniazid, pyrazinamide, ethambutol, and moxifloxacin daily for 2 months, followed by rifampicin, isoniazid, and moxifloxacin daily for 2 months Rifampicin, isoniazid, pyrazinamide, ethambutol, and moxifloxacin daily for 2 months, followed by rifampicin, isoniazid, and moxifloxacin thrice weekly for 2 months Rifampicin, isoniazid, pyrazinamide, ethambutol, and moxifloxacin daily for 2 months, followed by rifampicin, isoniazid, ethambutol, and moxifloxacin thrice weekly for 2 months Control (6‐month regimen): N = 172 randomized: 8 exclusions; 164 (95%) evaluated of those randomized Rifampicin, isoniazid, pyrazinamide, and ethambutol thrice weekly for 2 months, followed by rifampicin and isoniazid thrice weekly for 4 months Dosage: rifampicin 450 (< 60 kg) or 600 mg (> 60 kg); isoniazid 300 mg (daily) and 600 mg (thrice weekly); pyrazinamide 1500 mg; ethambutol 800 mg (daily) and 1200 mg (thrice weekly); moxifloxacin 400 mg
Outcomes	Outcomes reported and used in this review: Sputum culture conversion at 2 months of treatment (assessed at 5 months) Adverse reactions while on anti‐tuberculosis drugs Outcomes sought for the review but not reported: Relapse rates 24 months after treatment among those with a favourable or doubtful bacteriologic response at end of treatment (primary outcome for the ongoing trial) Death from any cause Failure to complete treatment Treatment failure (bacteriologic response at end of treatment is an outcome in the ongoing trial) Acquired drug resistance
Notes	Funding: Indian Council of Medical Research Follow‐up method: over the 24‐month follow‐up period, participants had monthly clinical examination and adherence and adverse events recording; monthly sputum microscopy and culture (and on days 15 and 45) and monthly drug susceptibility testing for 1 positive culture; monthly ECG, haemogram, liver and kidney functions, random blood sugars, and HIV ELISA tests. Chest X‐ray after the 2‐month intensive phase. Adverse events were assessed monthly for the duration of treatment (3 to 6 months) Treatment supervision: during the daily phase, treatment was under direct observation on 5 of 7 days of the week, whereas 2 doses were self‐administered. All thrice‐weekly phase doses were directly observed. Patients who missed treatment visits were visited at home and were motivated to attend the clinic for treatment Trial registration ID: CTRI 2008/091/000024 (retrospectively registered on 09/05/2008) Comment: results for sputum conversion at 2 months presented are the combined results of the 4 moxifloxacin regimens. Results for adverse events include up to the end of the 3‐ or 4‐month moxifloxacin regimens and over 6 months in the control regimen
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from report: "Restricted random allocation sequences generated using random number tables,separately for the 6 strata, were used to assign the regimens"
Allocation concealment (selection bias)	Low risk	Quote from trial registration document: "Sequentially numbered, sealed, opaque envelopes"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	This was an open‐label study but all treatment arms had supervised treatment and scheduled assessments for efficacy and safety outcomes
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The outcomes reported are sputum culture results at 2 months and drug adverse events that were assessed for all participants at specified time points. Sputum culture results and ECG reports are objective outcomes, and the likelihood of detection bias influencing the reporting of other adverse events is low
Incomplete outcome data (attrition bias): At the end of ATT (Treatment failure, positive sputum culture, treatment discontinuation, adverse events)	Low risk	590 of 616 (96%) on moxifloxacin regimens and 151 of 162 (93%) on the control regimen had sputum cultures reported at 2 months. The 3% differential attrition is unlikely to have influenced the difference in proportions with negative sputum cultures at 2 months of 14.6% (95% CI 8.8% to 21.8%)
Incomplete outcome data (attrition bias): At the end of follow‐up (Relapse, deaths)	Low risk	Not reported, as the trial is ongoing and this report includes only interim outcomes
Selective reporting (reporting bias)	Low risk	This is an interim report of an ongoing trial. The outcomes presented were pre‐stated in the trial registration document
Other bias	Low risk	No other sources of bias were detected

Abbreviations: ALT: alanine aminotransferase; ART: antiretroviral therapy; ARV: antiretroviral; AST: aspartate aminotransferase; ATT: anti‐tuberculosis treatment; CrCl: creatinine clearance; DM: diabetes mellitus; DMID: Division of Microbiology and Infectious Disease; ECG: electrocardiogram; ELISA: enzyme‐linked immunosorbent assay; IUCD: intrauterine contraceptive device; M tuberculosis: Mycobacterium tuberculosis; MDR‐TB: multi‐drug‐resistant tuberculosis; NIDDM: non‐insulin‐dependent diabetes mellitus; WHO: World Health Organization.