Dorman 2009.

Methods	Trial design: multicentre randomized placebo‐controlled double‐blind phase 2 clinical trial Follow‐up: 2 months Adverse event monitoring: assessed at baseline and weeks 2, 4, 6, and 8 of treatment: symptoms, blood tests for AST, bilirubin, creatinine, and complete blood count. Inclusion of all randomized participants in the final analysis: 105/433 (24.3%) excluded from final analysis
Participants	Number: 433 randomized; 328 evaluated Inclusion criteria: adults (age not specified) with suspected pulmonary TB and acid‐fast bacilli in a sputum specimen Exclusion criteria: history of > 7 days of antituberculous treatment within the previous 6 months or of fluoroquinolone treatment within the previous 3 months; pregnancy, or breastfeeding; initial sputum cultures negative for M. tuberculosis or resistance to isoniazid, fluoroquinolones, rifampicin, or pyrazinamide.
Interventions	Fluoroquinolone (moxifloxacin) substituted into regimen (replacing isoniazid) for 2 months (8 weeks) under direct observation 1. Moxifloxacin (400 mg daily) with an isoniazid placebo orally plus basic regimen (5 days a week or 7 days per week during the first two weeks) for 2 months (8 weeks) 2. Isoniazid (300 mg) plus moxifloxacin placebo daily orally 5 days a week (or 7 days per week during the first two weeks) for 2 months (8 weeks) plus basic regimen Basic regimen: rifampicin, pyrazinamide, ethambutol, and pyridoxine in accordance with published guidelines (Blumberg 2003)
Outcomes	1. Death from any cause: 3/219 versus 4/214 (intensive versus continuation phase) 2. TB‐related death: 2/219 versus 1/214 3. Sputum culture negative at 8 weeks: 99/219 versus 90/214 2. Time to sputum culture conversion (no numeric data provided) 3. Serious adverse events: 9/219 versus 8/214
Notes	Location: North America, Brazil, South Africa, Spain, and Uganda Setting: 26 Tuberculosis Trials Consortium (TBTC) sites HIV status: HIV‐positive participants (17/219 in study group fluoroquinolones + RZE, 18/214 in control group HRZE) Resistance: 13/219 in fluoroquinolones + RZE group, 14/214 in HRZE group); full susceptibility not confirmed: 13/219 in fluoroquinolones + RZE group, 6/214 in HRZE group Dates: no mention in the trial report Funding: CDC and the Global Alliance for Tuberculosis Drug Development. Bayer Pharmaceuticals provided moxifloxacin and moxifloxacin placebo tablets. Three out of 19 authors had a financial relationship with a commercial entity that had an interest in the subject of the manuscript.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study report specified "randomly assigned" but did not mention the method of randomization. "Randomisation was stratified by the presence of cavitation on baseline chest radiograph and continent of enrolment (Africa or not Africa); randomisation was not restricted within strata".
Allocation concealment (selection bias)	Unclear risk	Not described.
Blinding of participants/personnel (efficacy outcomes);performance bias All outcomes	Low risk	Double dummy placebo control was used. Review authors judged that efficacy outcomes were unlikely to have been influenced by a lack of blinding.
Blinding of participants/personnel (safety outcomes);performance bias All outcomes	Low risk	Double dummy placebo control was used. Review authors judged that safety outcomes were unlikely to have been influenced by a lack of blinding.
Blinding of outcome assessment (efficacy outcomes);detection bias All outcomes	Low risk	Double dummy placebo control was used. Laboratory staff assessing bacteriological outcomes were likely blinded to the treatment assignment.
Blinding of outcome assessment (safety outcomes);detection bias	Low risk	Double dummy placebo control was used. Review authors judged that safety outcomes were unlikely to have been influenced by a lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	High risk	105/433 (24.3%) excluded from final analysis. Quote: "Two efficacy analysis groups were prespecified. A modified ITT group excluded participants whose enrolment specimen failed to grow M. tuberculosis or had proven resistance to isoniazid, rifampin, pyrazinamide, ciprofloxacin, or ofloxacin; and enrollees whose treatment was incorrectly allocated. A protocol‐correct (PC) group excluded participants whose enrolment specimen failed to grow M. tuberculosis or was not proven susceptible to isoniazid, rifampin, pyrazinamide, ciprofloxacin, and ofloxacin; whose treatment was incorrectly allocated; who had contaminated week‐8 cultures; who died during intensive phase; who required more than 700 days to complete the study intensive‐phase treatment; or who took non study therapy for more than 14 days during the intensive phase. For safety analyses, all participants who received at least one dose of study treatment were included".
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement.
Other bias	Unclear risk	Three out of 19 authors had a financial conflict of interest. Bayer Pharmaceuticals provided moxifloxacin and moxifloxacin placebo tablets.