This study compares the ability of 2 semiautomated methods with a fully automated method for QT measurement to minimize the sample size required to detect a moxifloxacin effect and exclude a placebo effect in a thorough QT/QTc study. The fully automated and 1 of 2 semiautomated methods used a global QT measurement in 12 leads, whereas the other semiautomated method used a tangent method on single lead raw complexes. Mean QTcF intervals were greater when measured on a global QT electrocardiogram than on raw complexes, but the mean magnitudes of DeltaQTcF were similar for all methods. The 3 methods detected a statistically significant increase in QTcF for moxifloxacin compared to placebo and were able to exclude a placebo effect on QTcF in all 62 participants. However, due to a smaller variability, the semiautomated methods allowed these detections with fewer than 20 participants, whereas the fully automated required at least 27 participants.

The effect of beta-adrenergic blockade on QTc duration is different in LQT1 and LQT2 patients. Our data suggest that, in LQT1 patients, the well-known positive effect of beta-blockade might be associated with a prolongation of QTc duration. The mechanisms of beta-blockade protection may be different in LQT1 and in LQT2 patients.

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