Early cardiac safety of the 9-11 month Short course regimen for MDR-TB treatment
Annotatsiya
Background: Only 48% of multidrug resistant tuberculosis (MDR-TB) patients worldwide receive successful outcomes. Shorter, more effective regimens are required. The cardiac safety of the 9-11 month “Bangladesh regimen” has been largely unstudied. The regimen was piloted in Uzbekistan and as per WHO recommendations, electrocardiographic (ECG) monitoring was performed in the early phase of treatment. We aim, in this interim analysis, to describe the early cardiac safety of this regimen. Methods & Materials: Consecutively diagnosed MDR patients were recruited from Karakalpakstan, Uzbekistan. Moxifloxacin 400mg and clofazimine 100mg daily were included in the regimen. Patients had a single, 12 lead ECG performed at baseline, 2 and 4 weeks of therapy. RR and QT interval length was measured using lead II or V2 on the ECG printouts. QT was corrected using Fridericia's formula (QTcF). Data was prospectively collected using a standardised database (Koch 6, MSF, Paris) and analysed using openEpi (Ver 3.03, accessed 26/7/2015). Results: Between September 2013 and March 2015, 146 patients were enrolled. No patients were excluded from the study due to baseline cardiac findings or QT prolongation. Of these, 121 had ECGs performed per protocol and available for analysis. 27 (22.3%) were over 50 years of age and six had a reported history of cardiac disease. 12 patients (9.9%) had increases >60 ms from baseline with 1 patient showing an increase at both time points. Only one of these patients had QTcF increased over 450 ms. No patients had QTcF >500 ms during the screening period. No patients reported syncope or seizures and there were no deaths during the screening period. Univariate analysis of those with QT prolongation versus no QT prolongation did not identify other significant risk factors. Table 1 - ECG data Table 2 - Univariate analysis of cohort with QT prolongation vs. no QT prolongation Conclusion: Our results suggest that a 9-11 month regimen has acceptable early cardiac safety. As expected, QTcF is prolonged, the significance of which in MDR-TB patients requires further investigation.