Correction for QT/RR Hysteresis in the Assessment of Drug-Induced QTc Changes-Cardiac Safety of Gadobutrol
Correction for QT/RR Hysteresis in the Assessment of Drug-Induced QTc Changes-Cardiac Safety of Gadobutrol
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DOI：
10.1111/j.1542-474x.2009.00304.x
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发表时间：
2009-07-01
影响因子：
1.9
通讯作者：
Smetana, Peter
中科院分区：
文献类型：
--
作者：
Malik, Marek;Hnatkova, Katerina;Smetana, Peter
方法：将其用于钆布醇的TQT研究。TQT研究是一项随机、双盲、5次交叉研究，采用3种剂量的钆布醇（0.1、0.3和0.5 mmol/kg），安慰剂和阳性效应对照（利多卡因400 mg）。本研究入组了50例健康受试者，并提供了所有阶段的数据。根据研究前运动试验ECG评估QT/RR滞后。除其他外，人口之间的心率校正没有滞后的考虑，并结合人口的心率和滞后correction.Results：最高的心率增加（安慰剂和基线对照）的13.1次/分钟（90%CI 9.9-16.4）发生在1分钟后，管理的最高剂量的钆布醇。不考虑滞后，最高Δ Δ QTc为9.91 ms（90%CI 8.01-11.81），而滞后校正，这些值为7.62 ms（90%CI 6.37-8.87），从而将一个轻微的积极TQT研究变成一个负面的finding.Conclusion：因此，省略滞后校正从发作的快速心率变化可能会导致不正确的结论。尽管有显著的心率加速，但准确的滞后校正证实，钆布醇对心脏复极没有任何影响，这将在监管相关性的限度内.Ann Noninvasive Electrocardiol 2009;14（3）：242-250.
Methods: This was used in a TQT study of gadobutrol. The TQT study was a randomized double-blind five-times crossover study of three doses of gadobutrol (0.1, 0.3, and 0.5 mmol/kg) that was placebo and positive effect controlled (moxifloxacin 400 mg). The study enrolled 50 healthy subjects with data of all periods. QT/RR hysteresis was assessed from prestudy exercise test ECGs. Among others, comparisons were made between population heart rate correction without hysteresis considerations and combined population heart rate and hysteresis correction.Results: The highest heart rate increase (placebo and baseline controlled) of 13.1 beats per minute (90% CI 9.9-16.4) occurred 1 minute after the administration of the highest dose of gadobutrol. Without hysteresis consideration, the highest delta delta QTc were 9.91 ms (90% CI 8.01-11.81) while with hysteresis correction, these values were 7.62 ms (90% CI 6.37-8.87), thus turning a marginally positive TQT study into a negative finding.Conclusion: Hence, omitting hysteresis correction from episodes of fast heart rate changes may lead to incorrect conclusions. Despite substantial rate acceleration, accurate hysteresis correction confirms that gadobutrol does not have any effects on cardiac repolarization that would be within the limits of regulatory relevance.Ann Noninvasive Electrocardiol 2009;14(3):242-250.