Bartacek 2009.

Methods	Design: open, multicentre, multinational RCT Generation of allocation: generated by computer by an independent central randomization institute Allocation concealment: sealed, serially numbered, opaque randomization envelopes Blinding: none Duration: not mentioned
Participants	Number of participants: 1159 randomized Males: 68% (per‐protocol population) Inclusion criteria: new pulmonary tuberculosis (TB) participants, aged 15 years or more with at least 2 sputum specimens positive for acid‐fast bacilli (AFB) on direct smear microscopy or 1 sputum specimen positive for AFB on direct microscopy and postero‐anterior chest X‐ray consistent with pulmonary TB; with written informed consent form to participate in the study and willingness to comply with the protocol Exclusion criteria: a body weight < 30 kg, known or suspected hypersensitivity to rifamycins and/or to isoniazid, and/or to pyrazinamide and/or to etambutol hydrochloride and/or any of excipients; history of drug‐induced hepatitis; suspected or known as case of acute and chronic liver disease regardless of their origin; suspected or known as case of renal failure; suspected or known as case of peripheral optic neuritis, acute gouty arthritis (on clinical diagnosis), or history of gout; TB meningitis; any conditions (except HIV infection) that might prove fatal during the study (for example, metastatic cancer); poor general condition requiring additional measures to ensure survival; immunosuppressive treatment (for example, corticosteroids) during the whole study period; history of alcohol or drug abuse and history of psychiatric illness likely to lead to uncooperative behaviour, or pregnancy Completeness of follow‐up: 60.7% of participants (per‐protocol population) Baseline drug susceptibility test: results not reported HIV status: included only 6 HIV‐positive participants; 1 in the 4FDCs group and 5 in the single‐drug formulations group
Interventions	Six months treatment regimen (2HRZE/4HR) Intervention: 4 fixed‐dose combinations (FDCs) FDC tablets: Rimstar® (isoniazid 75 mg, rifampicin 150 mg, pyrazinamide 400 mg, and ethambutol 275 mg per tablet) given for the first 2 months (intensive phase), followed by Rimactazid® (isoniazid 75 mg and rifampicin 150 mg) for the succeeding 4 months (continuation phase) (N = 582). Doses used: "on the basis of body weight according to the international recommendations (WHO and International Union Against Tuberculosis and Lung Disease [The Union])" (Blomberg 2001) Control Single formulations of the same drugs in both phases (intensive and continuation) (N = 577). Doses used: the trial authors stated: "according to the national treatment standards of each respective country" The mean daily dosage of H, Z, and E at intensive phase in FDCs group was lower compared with single‐drug formulations group, the R dose were similar in both groups. Drugs were taken daily and according to the body weight for the total of participants, for whole treatment Mode of drugs administration: it was not reported whether the treatment was self‐administered or supervised
Outcomes	Outcomes used in this review Sputum smear conversion rate at 2 and at 6 months after initiation of treatment. Treatment failure. Relapse rate at months 12. Adverse events: serious; those leading to discontinuation of therapy and other adverse events. Death. Patient satisfaction with tablets: problems on swallowing, convenient number of tablets, and acceptable taste.
Notes	Locations: Egypt, Indian, Pakistan, the Philippines, and Thailand Setting: not described Source of funding: not mentioned Comments: follow‐up duration was 12 months after initiation of treatment. Sputum smear conversion rate was measured at 2, 4, 6, 9, and 12 months after initiation of treatment. Adverse events were assessed at each visit. Participant satisfaction with tablets was noted at 2 months
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using a computer random number generator.
Allocation concealment (selection bias)	Low risk	Central randomization institute which provided sequentially numbered, opaque, sealed envelopes.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	No blinding, but outcomes were unlikely to be influenced by lack of blinding (objective and measurable outcomes).
Blinding of outcome assessment (detection bias) All outcomes	Low risk	No blinding of outcome assessment, but outcome measurement is unlikely to be influenced by lack of blinding (objective and measurable outcomes).
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data.
Selective reporting (reporting bias)	Low risk	Most of expected outcomes are included in the published report.
Other bias	Low risk	The study appears to be free of other sources of bias.