The effects of bedaquiline, delamanid, and pretomanid on QT interval prolongation among patients with tuberculosis: A systematic review and meta-analysis
Abstract
INTRODUCTION Certain anti-tuberculosis drugs, i.e. bedaquiline (BDQ), pretomanid (Pa), and delamanid (DLM) have been shown to prolong corrected QT interval (QTc), which can be fatal.We aimed to estimate the incidence and risk of QTc prolongation among tuberculosis patients receiving either BDQ, DLM, or Pa alone or in combination.METHODS This meta-analysis systematically explored seven electronic databases (Clinicaltrials.gov,Cochrane CENTRAL, Embase, PROQUEST, PubMed, ScienceDirect, and SinoMed).Studies considered eligible if they were randomized clinical trials (RCTs) or non-randomized clinical trials (NRCTs) assessing QTc interval prolongation in patients receiving BDQ, DLM, and/or Pa, non-clinical trial study designs and studies of non-tuberculous mycobacterial infection were excluded.Risk of bias was assessed using the Delphi list for the RCTs and the Newcastle-Ottawa Scale for the NRCTs.Main outcomes were the incidence and risks compared to standard of care (SOC) of grades 3 and 4 QTc prolongation and the mean change of QTc interval (milliseconds).Limitations include inadequate subgroup analysis for potentially important and relevant confounders, variability in the period of drug administration, follow-up duration, as well as the incorporation of NRCTs.RESULTS Eighteen trials were eligible out of 1184 retrieved records.Combination therapy was associated with higher incidence of grade ≥3 QTc prolongation (BDQ+DLM 25.0%; BDQ+Pa 7.3%) compared with single-drug use (DLM…
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