QT Changes of Unforeseen Section Implications and Bedaquiline: An Observational Study

Abstract

Introduction: Bedaquiline (BDQ), a diarylquinoline class of antimicrobial, is one of the latest anti-mycobacterial agents to be developed in several decades. Despite the drug being a great hope for the Drug Resistant Tuberculosis (DR-TB) patients, previous studies have raised alarm about BDQ-induced QT prolongations of serious clinical implication. Unfortunately, knowledge about adverse drug reaction of BDQ on Indian patients remains limited. Therefore, dedicated research focused on safety of BDQ in Indian population can provide valuable insight. Aim: To assess the short-term safety of BDQ on Indian DR-TB patients. Materials and Methods: This prospective observational study was conducted over a period of one year on the DR-TB patients under BDQ therapy. Data of all the DR-TB patients from the first 14 days of BDQ therapy were enrolled in the study. All adverse events during this period were closely observed and recorded. Electrocardiography (ECG) were recorded daily during this period. From the observed QT value, a ‘corrected QT’ (QTc) value was calculated using Fridericia’s formula (QTcF). Values above 440 ms were noted as prolonged QTcF and values >500 ms were given a special consideration. Results: Total 49 patients were recruited in this study, with mean age of 38.63±1.63 years. A total of 124 reports of adverse events or symptoms were recorded during the 14 days in-hospital period. Nausea was the most commonly reported complaint (n=33) followed by headache (n=30) and arthralgia (n=28). A total of 278 observations of prolonged QTcF values (>440 ms) was noted out of 686 ECG recordings. The mean QTcF values among day 1, day 7 and day 14 showed statistically significant difference {p=0.01, 95% CI (Confidence Interval)}. Moreover, a mean increase of 14.2% was observed in the QTcF values between day 1 and day 14. There were a total of 69 observations of QTcF value more than 500 ms. The incidence of such value was maximum on day 14 (n=9). The QTcF values were found to follow three distinct trends: a) Initial rise then fall (n=9), b) Initial fall and then rise (n=10) and c) Rise followed by further rise (n=30). Conclusion: The present observational study was targeted to detect the short-term safety of BDQ in the DR-TB patients during the initial 14 days of therapy. The patients complained of several non serious adverse effects. Three distinct patterns of QT changes and reduction of QTcF values were relatively new findings with the merit for further investigation. However, a longer perspective of adverse events was beyond the scope of this study.