Table 5.

Definitions for primary outcome status.

Each participant will be classified into one of the following 3 outcome categories of Absence of Cure (Unfavorable Outcome), Cure (Favorable Outcome), or Not Assessable. The primary efficacy outcome will be assessed at 12 months after treatment assignment; a secondary efficacy outcome will consider the follow-up period to be 18 months after treatment assignment.

Absence of cure (unfavorable outcome) is assigned to a participant who meets any one or more of the following criteria:

• Absence of bacteriological cure. A participant will be considered to have absence of bacteriological cure if he/she has a sputum sample, obtained at or after Week 17, that is culture positive for an M. tuberculosis strain that is indistinguishable from the initial isolate, and this is confirmed by a second sample that is culture positive for M. tuberculosis. A second confirmatory sample is required as a single positive sputum culture in isolation will not be considered absence of bacteriological cure.

• Participants who die from any cause during study treatment, except from violent or accidental cause (e.g. road traffic accident).

• Participants failing to complete treatment and not assessable at the end of the follow-up period.

• Participants who had a positive culture for M. tuberculosis when last seen, whether confirmed by a second sample or not, unless determined to have been re-infected

• Participants receiving any one or more of the following: a) extension of treatment beyond that permitted by the protocol; b) a re-start of treatment; c) a change in treatment for any reason except re-infection, pregnancy, or temporary drug challenge

Cure (favorable outcome) is assigned to a participant who meets any one of the following criteria and has not already been classified as having an unfavorable outcome:

• Participants with negative cultures at the end of the follow-up period

• Participants who at the end of the follow-up period are clinically without symptoms/signs of ongoing active TB and are unable to produce a sputum specimen

• Participants who at the end of the follow-up period are clinically without symptoms/signs of ongoing active TB and produce a sputum specimen that is contaminated without evidence of M. tuberculosis

An outcome of Not Assessable is assigned to a participant meeting any one or more of the following criteria and not already classified as having an unfavorable outcome:

• Participants who completed assigned treatment and then default from follow-up, with their last culture being negative for M. tuberculosis

• Women who become pregnant during their assigned active treatment and stop their assigned treatment

• Participants who die during the follow-up phase (≥ 15 days after completion of study treatment)

• Participants who die from a violent (e.g. homicide) or accidental (e.g. road traffic) cause during their assigned active treatment. As above, suicide will be considered an unfavorable outcome

• Participants re-infected with a new strain of M. tuberculosis, demonstrated to be different from that identified at study entry through genotyping methods