This work was funded by the National Institute for Health through the R01HL084402 award.
Highly Automated QT Measurement Techniques in 7 Thorough QT Studies Implemented under ICH E14 Guidelines
Article first published online: 20 JAN 2011
©2011, Wiley Periodicals, Inc.
Annals of Noninvasive Electrocardiology
Volume 16, Issue 1, pages 13–24, January 2011
How to Cite
Couderc, J.-P., Garnett, C., Li, M., Handzel, R., McNitt, S., Xia, X., Polonsky, S. and Zareba, W. (2011), Highly Automated QT Measurement Techniques in 7 Thorough QT Studies Implemented under ICH E14 Guidelines. Annals of Noninvasive Electrocardiology, 16: 13–24. doi: 10.1111/j.1542-474X.2010.00402.x
- Issue published online: 20 JAN 2011
- Article first published online: 20 JAN 2011
- thorough QT study;
- drug cardiotoxicity;
- QT interval;
- drug safety
Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic-QT interval measurement (HA-QT) method. We applied a HA-QT method to the data from 7 TQT studies. We investigated both the placebo and baseline-adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin-induced QTc prolongation in one study as well. The absolute HA-QT data were longer than the FDA-approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 ± 24 ms on drug and 9.8 ± 25 ms on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4 ± 2.8 ms, P = 0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1 ± 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods.
Ann Noninvasive Electrocardiol 2011;16(1):13–24