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Clinical Trial
. 2022 Apr 1;26(4):334-340.
doi: 10.5588/ijtld.21.0403.

QT prolongation in the STREAM Stage 1 Trial

G Hughes  1 , H Bern  1 , C-Y Chiang  2 , R L Goodall  1 , A J Nunn  1 , I D Rusen  3 , S K Meredith  1
Affiliations
Clinical Trial

QT prolongation in the STREAM Stage 1 Trial

G Hughes et al. Int J Tuberc Lung Dis. .

Abstract
in English, French

BACKGROUND: STREAM (Standardized Treatment Regimen of Anti-TB Drugs for Patients with MDR-TB) Stage 1 demonstrated non-inferior efficacy of a shortened regimen (the Short regimen) for rifampicin-resistant TB (RR-TB) compared to the contemporaneous WHO-recommended regimen. This regimen included moxifloxacin and clofazimine, known to cause QT prolongation, and severe prolongation was more common on the Short regimen. Here we investigate risk factors for QT prolongation with the Short regimen.METHODS: Data from patients prescribed the Short regimen (n = 282) were analysed to identify risk factors for severe QT prolongation (QT/QTcF ≥500 ms or ≥60 ms increase in QTcF from baseline).RESULTS: Of the 282 patients on the Short regimen, 94 (33.3%) developed severe QT prolongation: 31 QT/QTcF ≥500 ms; 92 experienced ≥60 ms QTcF increase from baseline. The median time to QT/QTcF ≥500 ms was 20 weeks (IQR 8-28), and the time to ≥60 ms increase from baseline was 18 weeks (IQR 8-28). Prolongation ≥500 ms was most frequent in patients from Mongolia (10/22, 45.5%) compared with 3.5-11.9% at other sites, P < 0.001. Higher baseline QTcF increased risk of prolongation to ≥500 ms (QTcF ≥400 ms: OR 5.99, 95% CI 2.04-17.62).CONCLUSION: One third of patients on the Short regimen developed severe QT prolongation. QT/QTcF ≥500 ms was more common in patients from Mongolia and in those with a higher baseline QTcF, which may have implications for implementation of treatment.

CONTEXTE :: L’essai clinique STREAM (Standardized Treatment Regimen of Anti-TB Drugs for Patients with MDR-TB)Étape 1 a démontré l’efficacité non inférieure d’un schéma plus court pour le traitement de la TB résistante à la rifampicine (RR-TB) par rapport au schéma recommandé par l’OMS. Ce schéma comprenait moxifloxacine et clofazimine, connues pour provoquer un allongement de l’intervalle QT. Les cas graves d’allongement de l’intervalle QT étaient plus fréquents sous schéma court. Nous avons analysé les facteurs de risque d’allongement de l’intervalle QT chez les patients sous schéma court.

MÉTHODES :: Les données des patients randomisés sous schéma court (n = 282) ont été analysées pour identifier les facteurs de risque de grave allongement de l’intervalle QT (QT/QTcF ≥500 ms ou augmentation ≥60 ms de l’intervalle QTcF par rapport à l’inclusion).

RÉSULTATS :: Ont été associés 94 (33,3%) patients sous schéma court à un grave allongement de l’intervalle QT : 31 cas de QT/QTcF ≥500 ms ; 92 cas d’augmentation ≥60 ms de l’intervalle QTcF par rapport à l’inclusion. Le temps médian avant QT/QTcF ≥500 ms était de 20 (IQR 8–28) semaines et de 18 semaines (IQR 8–28) avant augmentation ≥60 ms par rapport à l’inclusion. Un allongement ≥500 ms était plus fréquent chez les patients de Mongolie (10/22, 45,5%), par rapport à 3,5–11,9% pour les autres pays (P < 0,001). Un intervalle QTcF plus élevé à l’inclusion augmentait le risque d’allongement ≥500 ms (QTcF ≥400 ms : OR 5,99, IC 95% 2,04–17,62).

CONCLUSION :: Un tiers des patients sous schéma court ont été associés à un grave allongement de l’intervalle QT. Un intervalle QT/QTcF ≥500 ms était plus fréquent chez les patients de Mongolie et chez ceux dont l’intervalle QTcF était plus élevé à l’inclusion, ce qui pourrait impacter l’instauration du traitement.

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Conflict of interest statement

Conflicts of interest: none declared.

Figures

Figure 1
Figure 1
Mean QTcF by visit and allocated treatment arm.
Figure 2
Figure 2
Mean change in QTcF from baseline by visit and allocated treatment arm. Mean QTcF and mean change in QTcF presented with error bars detailing ± 1 standard error of the mean.
Figure 3
Figure 3
Kaplan–Meier plot of time to exceeding maximum QT/QTcF of 500 ms post baseline.
See this image and copyright information in PMC

Comment in

References

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