Trial reportAnnals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc2009
Correction for QT/RR hysteresis in the assessment of drug-induced QTc changes--cardiac safety of gadobutrol.
Trial report in Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- Randomized study of the effect of gadopiclenol, a new gadolinium-based contrast agent, on the QTc interval in healthy subjects.British journal of clinical pharmacology · 2020Trial
- Comparison of Digital 12-Lead ECG and Digital 12-Lead Holter ECG Recordings in Healthy Male Subjects: Results from a Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2016Trial
- Unexpected Ventricular Fibrillation During a Cardiovascular Magnetic Resonance Examination Documented With Simultaneous Quantitative Myocardial Perfusion.JACC. Case reports · 2025Article
- Detection of T Wave Peak for Serial Comparisons of JTp Interval.Frontiers in physiology · 2019Article
- Errors of Fixed QT Heart Rate Corrections Used in the Assessment of Drug-Induced QTc Changes.Frontiers in physiology · 2019Article
- Post-marketing surveillance of gadobutrol for contrast-enhanced magnetic resonance imaging in Japan.Japanese journal of radiology · 2018Article
- Gadobutrol: A Review in Contrast-Enhanced MRI and MRA.Clinical drug investigation · 2018Review
- Importance of QT/RR hysteresis correction in studies of drug-induced QTc interval changes.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Categorization and theoretical comparison of quantitative methods for assessing QT/RR hysteresis.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2017Review
- Gadobutrol in India-A Comprehensive Review of Safety and Efficacy.Magnetic resonance insights · 2017Review
- Drug-Induced QT/QTc Interval Shortening: Lessons from Drug-Induced QT/QTc Prolongation.Drug safety · 2016Review
- QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2016Article
- The application of root mean square electrocardiography (RMS ECG) for the detection of acquired and congenital long QT syndrome.PloS one · 2014Article
- Conventional QT variability measurement vs. template matching techniques: comparison of performance using simulated and real ECG.PloS one · 2012Article
- Review
- Slow QT interval adaptation to heart rate changes in normal ambulatory subjects.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2011Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe so-called thorough QT/QTc (TQT) studies required for every new pharmaceutical compound are negative if upper single-sided 95% confidence interval (CI) of placebo and baseline corrected QTc prolongation is <10 ms. This tight requirement has many methodological implications. If the investigated drug has a fast action and ECGs cannot be obtained at stable heart rates, QT/RR hysteresis correction is needed.
methodsThis 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.
resultsThe 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 DeltaDeltaQTc 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.
conclusionHence, 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.
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