Session P94.1

Comparison of Automatic versus Manual QT Methods for the Detection of Moxifloxacin-Induced Prolongation of the QTc Interval

RH Handzel*, JP Couderc

University of Rochester Medical Center
Rochester, NY, USA

Background: The Food and Drug Administration (FDA) of the U.S. Human Health Department requires that any new pharmaceutical compound has to be checked for its potential QT prolonging effect on the surface ECG. As today, fully manual and semi-computerized measurements of QT intervals are standard techniques used in drug safety trials. In this study, we investigated an automatic technique for measuring the QT/QTc interval in a large set of 12-lead ECG strips and we compared the drug-concentration profile of computerized QTc to the results submitted to the Agency.
Methods: We analyzed 8, 911 ECG tracings from 66 healthy individuals who took part in a longitudinal four-arm crossover study. The ECGs are from a thorough QT study stored and were extracted from the ECG FDA Warehouse. Moxifloxacin was used as a positive control substance for QT prolongation. The RR and QT intervals were measured in lead II using the COMPAS software that was developed at the University of Rochester, Rochester, NY, USA. This software used a modified version of the tangent method for identifying the end of the T-wave. The QT interval for each beat was corrected for its dependence on heart rate using the Fridericia’s correction (QTfc). We computed the profile of moxifloxacin-induced QT prolongation based on delta delta QTfc=mean[QTfc(moxi-t0)-QTfc(placebo-t0)]. t0 is the baseline value corresponding to the ECGs taken just prior to both treatments.
Results: The automatic and manual QTc interval measurements were not statistically different when describing the effect of moxifloxacin on this interval across time. At the drugs maximum concentration the automatic measurements yielded a delta delta QTfc value of 14.9±3.0 ms and the manual method produced a delta delta QTfc of 12.8±2.6 ms.
Conclusion: Using computerized measurements of the QT interval offers many advantages regarding time and cost of conducting drug safety trials. This study strongly supports the ability of an automatic algorithm to measure moxifloxacin-induced QT prolongation with the same level of precision than manual measurements currently reported to regulatory agencies.

(Abstract Control Number: 4)