QT prolongation in participants receiving bedaquiline-containing regimens: analysis of data from Phase 3 STREAM Stage...

Multidrug-resistant TB regimens are associated with higher risk of QT prolongation; understanding bedaquiline's (BDQ) role is crucial for safety and management.

We report a pre-specified secondary analysis of data from STREAM Stage 2 (ISRCTN18148631), a Phase 3, non-inferiority trial evaluating BDQ-containing regimens in participants aged ≥15 years with multidrug/rifampicin-resistant TB. Participants were randomised to one of four regimens (two BDQ-containing and two BDQ-free). Electrocardiogram assessments were routinely conducted through Week 76, with continued monitoring for significant QT prolongation. Averaged Fridericia's corrected QT interval (QTcF) results are reported.

Of 588 participants, median age was 32.7 years (range 16-69) and 236 (40%) were female. QTcF gradually increased from baseline to Weeks 10-14, plateaued, then decreased during treatment. Mean QTcF change for BDQ regimens was <10 ms higher than control at all timepoints. Risk of experiencing at least one QTcF ≥500 ms was similar between control and 40-week oral BDQ regimen (hazard ratio 1.43, 95% confidence interval: 0.66-3.11).

BDQ was associated with mean QTcF prolongation of <10 ms, which was not more than additive to other drugs. Rates of QTcF ≥500 ms were comparable between BDQ-containing and BDQ-free arms, indicating comparable incidences of this event within the study context.