QT prolongation in participants receiving bedaquiline-containing regimens: analysis of data from Phase 3 STREAM Stage 2
Abstract
Background: Multidrug-resistant TB regimens are associated with higher risk of QT prolongation; understanding bedaquiline's (BDQ) role is crucial for safety and management.
Methods: 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.
Results: 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).
Conclusion: 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.
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 588 participants or records.
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