Criteria for discontinuing or modifying allocated interventions {11b}
TB, diaphoresis, Tremor, fever, fatigue, Hypertonia, rash, pain, eosinophilia, hyperreflexia, agitation, nausea,, tenderness, hypertension
HYPERTENSION, EOSINOPHILIA
Besides withdrawal of consent, requiring medication prohibited by protocol or sponsor decision, several stopping criteria for participants’ safety are in place:• A participant should discontinue study drug if:◦ ALT or AST >8×ULN ◦ ALT or AST >5×ULN for more than 2 weeks ◦ ALT or AST >3×ULN and (total bilirubin (TBL) >2×ULN or INR >1.5 ◦ ALT or AST >3×ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%) • severity grading for the QTcF interval on-treatment ECGs, adapted from [• • BP systolic >160 mmHg, or diastolic >100 mmHg: ◦ Re-assessment: Participants who develop significant hypertension with systolic blood pressure (BP) averages of three measurements of ≥ 160 mm Hg, and/or diastolic BP of ≥ 100 mm Hg, but less than 180/110 mmHg, will be re-assessed on 2 separate occasions.◦ They should be re-counselled as to the foods and drink to be avoided with study treatment, as non-compliance to this could be an important aspect to the hypertension.◦ If this evaluation supports the conclusion of a significant increase in blood pressure, the investigator will assess potential causes. If the increase is determined to be associated with study treatment, a de-challenge/re-challenge will be performed: participants will discontinue DZD. If, after ≥ 10 h (> 5 × t◦ Treatment with BDQ, DLM and MXF should continue throughout.◦ Continued hypertension after re-assessment: participants who develop persistent hypertension ≥ 160/100 mmHg after evaluation and adequate antihypertensive treatment, including those who have undergone a re-challenge with DZD, will discontinue all study treatment and complete TB treatment according to national TB program guidelines. These participants will receive follow-up to determine whether the condition normalizes after discontinuation of study treatment.BP systolic >180 mmHg, or diastolic >110 mmHg:◦ Immediate stop• ◦ Spontaneous clonus◦ Inducible clonus PLUS agitation or diaphoresis◦ Ocular clonus PLUS agitation or diaphoresis◦ Tremor PLUS hyperreflexia◦ Hypertonia PLUS temperature above 38°C PLUS ocular clonus or inducible clonus• 