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Open Access QT prolongation in the STREAM Stage 1 Trial

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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.

Keywords: QTcF; clofazimine; electrocardiogram; moxifloxacin; rifampicin-resistant tuberculosis

Document Type: Research Article

Affiliations: 1: Medical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and Methodology, London, UK 2: Division of Pulmonary Medicine, Department of Internal Medicine, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan, Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France 3: Research Division, Vital Strategies, New York, NY, USA

Publication date: April 1, 2022

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