Risk factors for cardiac QT interval prolongation in patients with multidrug-resistant tuberculosis treated with a new 6-9-months regimen

Abstract

Background: From 2014 to 2022, the Mongolia site at the National Center for Communicable Diseases has been involved in the international, multi-center randomized controlled clinical trial aiming to reduce treatment duration for MDR TB (STREAM trials). A recent analysis of the STREAM Stage 1 trial revealed that 11% of patients on the shorter 9-month regimen with injectables experienced severe QT/QTcF prolongations, with the majority from the Mongolia site. In the Stage 2 trial, a central collection of routine blood tests, including electrolytes, and thyroid tests were collected, which could help to identify imbalances contributing to QT/QTcF prolongations. Identifying the risk factors for QT prolongation is essential evidence to provide guidance for the National TB Program and frontline TB clinicians. Aim: To determine the risk factors associated with QT prolongation among Mongolian participants with MDR TB treated with 6-9-month shortened novel treatment regimens. Materials and Methods: Among the 588 participants from 7 countries in the multi-center clinical trial, 28 cases of QT interval prolongation were identified, with 18 occurring in Mongolian participants. Analysis of severe QT prolongations in Mongolian participants unveiled a statistically significant association between elevated baseline QTcF (OR-1.09, 95% CI: 1.04-1.14; p<0.00) and baseline thyroid-stimulating hormone (OR-2.42, 95% CI: 1.01-5.75; p<0.05) levels and cardiac QT prolongation. Results: Among the 588 participants from 7 countries included in the multi-center clinical trial, 28 cases of QT interval prolongation were found, 18 of which were among Mongolian participants. Analysis of severe QT prolongations among the Mongolian participants revealed that higher baseline QTcF (OR-1.09, 95%CI:1.04-1.14; p<0.00), and baseline thyroid-stimulating hormone (OR-2.42, 95%CI:1.01-5.75; p<0.05) were statistically significantly associated with the cardiac QT prolongation. Conclusion: Severe cardiac QT interval prolongation occurred in 1/6 of patients during treatment and follow-up. Therefore, assessment of baseline cardiac QT/QTcF interval and baseline thyroid-stimulating hormone levels prior to initiation of shortened treatment for MDR TB may prevent severe QT prolongations during treatment and follow-up. Electrocardiography, careful monitoring of QT prolongation during treatment and follow-up, and implementing appropriate patient management strategies are imperative for ensuring successful treatment outcomes.