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Randomized Controlled Trial
. 2024 Apr;23(4):469-476.
doi: 10.1080/14740338.2024.2322116. Epub 2024 Mar 10.

T-wave morphology abnormalities in the STREAM stage 1 trial

Gareth Hughes  1 , William J Young  2   3 , Henry Bern  1 , Angela Crook  1 , Pier D Lambiase  4   5 , Ruth L Goodall  1 , Andrew J Nunn  1 , Sarah K Meredith  1
Affiliations
Randomized Controlled Trial

T-wave morphology abnormalities in the STREAM stage 1 trial

Gareth Hughes et al. Expert Opin Drug Saf. 2024 Apr.

Abstract

Background: Shorter regimens for drug-resistant tuberculosis (DR-TB) have non-inferior efficacy compared with longer regimens, but QT prolongation is a concern. T-wave morphology abnormalities may be a predictor of QT prolongation.

Research design and methods: STREAM Stage 1 was a randomized controlled trial in rifampicin-resistant TB, comparing short and long regimens. All participants had regular ECGs. QT/QTcF prolongation (≥500 ms or increase in ≥60 ms from baseline) was more common on the short regimen which contained high-dose moxifloxacin and clofazimine. Blinded ECGs were selected from the baseline, early (weeks 1-4), and late (weeks 12-36) time points. T-wave morphology was categorized as normal or abnormal (notched, asymmetric, flat-wave, flat peak, or broad). Differences between groups were assessed using Chi-Square tests (paired/unpaired, as appropriate).

Results: Two-hundred participants with available ECGs at relevant times were analyzed (QT prolongation group n = 82; non-prolongation group n = 118). At baseline, 23% (45/200) of participants displayed abnormal T-waves, increasing to 45% (90/200, p < 0.001) at the late time point. Abnormalities were more common in participants allocated the Short regimen (75/117, 64%) than the Long (14/38, 36.8%, p = 0.003); these occurred prior to QT/QTcF ≥500 ms in 53% of the participants (Long 2/5; Short 14/25).

Conclusions: T-wave abnormalities may help identify patients at risk of QT prolongation on DR-TB treatment.

Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02409290). Current Controlled Trial number, ISRCTN78372190.

Keywords: QTcF; Rifampicin-resistant tuberculosis; T wave morphology; clofazimine; electrocardiogram; moxifloxacin.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants, or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Examples of the different T-wave morphology that were categorized from participants in the STREAM stage 1 trial.
Figure 2.
Figure 2.
T-wave morphology abnormality by time point showing percentage of ECGs affected.
See this image and copyright information in PMC

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