Table 1.

Trial analysis populations and related unfavourable outcomes: list of definitions applied at end-point review for patients in the trial by analysis population *

Modified intention-to-treat population
All randomised patients included, except: Late exclusions due to resistance pattern, lack of culture confirmation, protocol violation at enrolment Patients who, having completed treatment, are lost to follow-up or withdrawn from the study with their last status being culture-negative Women who become pregnant during treatment and stop their allocated treatment Patients who died during treatment from violent or accidental cause Patients who died during follow-up (after the end of treatment) with no evidence of failure or relapse of their TB Patients who, after being classified as having culture-negative status, are re-infected with a strain other than that with which they had been originally infected Patients who are able to produce sputum at 12 months, but whose 12-month visit sputum samples are all contaminated or missing, who cannot be brought back for repeat culture testing† Unfavourable outcome definitions Patients not classified as having achieved or maintained culture-negative status when last seen Patients previously classified as having culture-negative status who, following the end of treatment, have two positive cultures without an intervening negative culture Patients who had a positive culture not followed by at least two negative cultures when last seen Patients dying from any cause during the 6-month treatment phase, except from violent or accidental cause (e.g., road traffic accident), not including suicide (e.g., suicide was considered an unfavourable outcome) Patients definitely or possibly dying from TB-related cause during the follow-up phase Patients requiring a restart or a change of treatment because of an unfavourable outcome with or without bacteriological confirmation, i.e., on bacteriological, radiographic or clinical grounds Patients requiring an extension of their treatment beyond that permitted by the protocol, a restart or a change of treatment for any reason except reinfection or pregnancy Patients failing to complete an adequate course of treatment, who were unassessable at 12 months Patients lost to follow-up or withdrawn from the study before the end of treatment
Per protocol population
All randomised patients included, except: Late exclusions due to resistance pattern, lack of culture confirmation, protocol violation at enrolment Patients who, having completed treatment, are lost to follow-up or withdrawn from the study with their last status being culture-negative Women who become pregnant during treatment and stop their allocated treatment Patients who died during treatment from violent or accidental cause Patients who died during follow-up (after the end of treatment) with no evidence of treatment failure or relapse of their TB Patients who, after being classified as having culture-negative status, are re-infected with a strain other than that with which they had been originally infected Patients who are able to produce sputum at 12 months, but whose 12-month visit sputum samples are all contaminated or missing, who cannot be brought back for repeat cultures† Patients lost to follow-up or withdrawn before the end of treatment† Patients whose treatment was modified or extended for reasons other than an unfavourable therapeutic response to treatment† Patients not meeting the definition of having received an adequate amount of their allocated study regimen (80% of treatment by self-reporting)† Patients who are classified as “major protocol deviations”† Unfavourable outcome definitions: Patients not classified as having achieved or maintained culture-negative status when last seen Patients previously classified as having culture-negative status who, following the end of treatment, have two positive cultures without an intervening negative culture Patients who had a positive culture not followed by at least two negative cultures when last seen Patients dying from any cause during the 6 month treatment phase, except from violent or accidental cause (e.g., road traffic accident), not including suicide (e.g., suicide will be considered an unfavourable outcome) Patients definitely or possibly dying from TB related cause during the follow-up phase Patients requiring a restart or a change of treatment because of an unfavourable outcome with or without bacteriological confirmation, i.e., on bacteriological, radiographic or clinical grounds

* Relapse was declared if positive cultures after the end of treatment were considered identical to the baseline sample using WGS (difference of <20 SNPs), or if WGS was not available. Recurrence was considered to be re-infection if the M. tuberculosis strain was different by >100 SNPs from the baseline strain.

^† Unless already declared as unfavourable.

WGS = whole-genome sequencing; SNP = single-nucleotide polymorphism.