Highly automated QT measurement techniques in 7 thorough QT studies implemented under ICH E14 guidelines.
Highly automated QT measurement techniques in 7 thorough QT studies implemented under ICH E14 guidelines.
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DOI：
10.1111/j.1542-474x.2010.00402.x
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Zareba W
中科院分区：
文献类型：
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作者：
Couderc JP;Garnett C;Li M;Handzel R;McNitt S;Xia X;Polonsky S;Zareba W
全面的QT （TQT）研究旨在评估一种新型药物对心脏心室复极过程的潜在影响，使用QTc延长作为点扭转的替代标志物。目前从数千张心电图中测量QT间期的过程既漫长又昂贵。在这项研究中，我们提出了一种高度自动化的QT间期测量（HA-QT）方法的验证。我们将HA-QT测量方法应用于7项TQT研究的数据。我们研究了在预期峰值浓度时，安慰剂和阳性对照药物莫西沙星（moxiflo沙星）诱导的基线调整QTc间期延长。比较分析还评价了莫西沙星诱导QTc延长的时间过程。HA-QT的绝对数据比fda批准的QTc数据更长。这一趋势在莫西沙星组和安慰剂组之间没有差异：药物组9.6±24msec，安慰剂组9.8±25msec。当比较安慰剂-基线调整的QTc延长时，两种方法的差异消失（1.4±2.8msec, p=0.4）。HA-QT与fda批准的测量方法之间的精度差异无统计学差异，为0.1±0.1msec （p=0.7）。此外，莫西沙星诱导的QTc延长的时间过程经安慰剂调整后在两种测量方法之间无统计学差异。
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 measurement method to the data from seven 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±24msec on drug and 9.8±25msec on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4±2.8msec, p=0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1±0.1msec (p=0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods.