Table 1 Study inclusion and exclusion criteria

• Documented pulmonary TB due to strains of Mycobacterium tuberculosis resistant to rifampicin and resistant to fluoroquinolones, by a validated rapid molecular test. In trial sites in countries with high background prevalence of fluoroquinolone resistance (India and Pakistan), an undefined^a result of a validated rapid molecular tests for fluoroquinolone resistance also permits inclusion. Patients with RR-TB who are unable to tolerate fluoroquinolones are also eligible, regardless of resistance or susceptibility to fluoroquinolones

• ≥ 15 years of age

• Willingness to use contraception

• Provision of informed consent for study participation

• Residence in a dwelling that can be located by study staff and an expectation to remain in the area for the duration of the study

• Patients with known allergies or hypersensitivity to any of the investigational drugs

• Patients known to be pregnant or unwilling or unable to stop breastfeeding an infant

• Patients unable to comply with treatment or follow-up schedule

• Patients with exposure (intake for 30 days or more) in the past 5 years to bedaquiline, delamanid, linezolid, or clofazimine, or with proven or likely resistance to bedaquiline, delamanid, linezolid, or clofazimine

• Patients who have received second-line drugs for 15 days or more prior to the screening visit date in the current MDR-TB treatment episode; exceptions include (a) patients who have experienced treatment failure, (b) patients who are restarting treatment after having been lost to follow-up, and (c) treatment adaptation to adapt to new WHO treatment recommendations

• Patients with one or more of the following laboratory results:

o Grade 3 or higher hemoglobin, calcium, magnesium, creatinine, or bilirubin

o Grade 2 or higher potassium, aspartate aminotransferase, alanine aminotransferase, or total bilirubin

o Grade 4 result on any other screening laboratory tests

• Patients with cardiac risk factors including ECG abnormalities (i.e. QTcF ≥ 450 ms), pacemaker implant, and personal history of cardiovascular disease (i.e. long QT syndrome, left or right bundle branch block) or family history of long QT syndrome

• Patients requiring continued use of a contraindicated medication

• Patients currently taking part in another trial of any medication used or being studied for TB treatment

• Patients with any condition (social or medical) which, in the opinion of the investigator, would make study participation unsafe