This data set, its source, and the methods used to generate it, are described in
ClinicalTrials.gov identifier: NCT02308748
When referencing this material, please include the citations above, and also include the standard citation for PhysioNet:
The ECGDMMLD database contains data from a randomized, double-blind, 5-period crossover clinical trial in 22 healthy male and female subjects, 18 to 35 years of age, to compare the electrophysiological response of hERG potassium channel blocking drugs with and without the addition of late sodium or calcium channel blocking drugs. The 5 treatment periods are 1) dofetilide alone, 2) mexiletine with and without dofetilide, 3) lidocaine with and without dofetilide, 4) moxifloxacin with and without diltiazem and 5) placebo. During each treatment period, 12 blood samples for pharmacokinetic measurements are obtained with matched 12-lead ECG recordings.
In each of the five treatment periods, the subjects were dosed three times during the day [Johannesen et al, Clin Pharmacol Ther. 2016]. Dofetilide (Tikosyn, Pfizer, New York, NY) and mexiletine (Teva Pharmaceuticals USA, North Wales, PA) were administered orally immediately after meals, whereas lidocaine (B. Braun Medical, Bethlehem, PA), moxifloxacin and diltiazem were administered intravenously. Intravenous infusions were split into a 60-minute loading dose followed by a 30-minute maintenance dose.
The primary pharmacokinetic samples were taken at the start and end of each of the three maintenance doses during the day (morning, afternoon and evening), as these were expected to be associated with highest plasma concentrations of both the oral and intravenously administered drugs. Additional pharmacokinetic samples were taken at 30 and 120 minutes poststart of intravenous dosing during each of the three dosing periods during the day. There was one week between treatment periods.
During each period, continuous ECGs were recorded at 500 Hz with an amplitude resolution of 2.5 μV using the Mortara Surveyor system (Mortara, Milwaukee, WI). From the continuous recording, triplicate 10‐second ECGs were extracted before the draw of each pharmacokinetic sample at 14 predefined time‐points: 1 point pre-dose (-0.5 h) and 13 points post‐dose (1.5, 2, 2.5, 3, 6.5, 7, 7.5, 8, 12, 12.5, 13, 13.5 and 24 h), during which the subjects were resting in a supine position for 10 minutes.
At each of the 14 time‐points, 3 optimal 10‐second 12‐lead ECGs were extracted with stable heart rates and maximum signal quality using Antares software (AMPS‐LLC, New York City, NY). The resulting ECGs were up‐sampled from 500 to 1000 Hz.
The raw directory contains the 4211 original extracted 10-second standard 12 lead ECG segments organized in subdirectories named after the subject number or randomization number
RANDID in the second column of the SCR-003.Clinical.Data.csv file. The ECGs are stored in standard MIT format, with a signal
.dat file and corresponding header
.hea file for each segment
The medians directory contains derived representative median beats for the raw ECG segments. Median beats were obtained as follows: the median PQRST waveform (median cardiac beat) for each lead was calculated by sample-by-sample synchronization of the QRS complex, and beats of a nonsinus origin were excluded based on a cross-correlation coefficient and RR interval history .
There are also semi-automatic annotations of each median beat based on the vector magnitude lead, containing P onset, QRS onset, QRS offset, T peak, secondary T peak (if present) and T offset. The annotations are stored in standard MIT annotation format, with annotator extension
The SCR-003.Clinical.Data.csv file contains demographic information about the subjects, and important metadata about each ECG recording including their time-point, dosing period, associated drug, various beat intervals, and morphology measurements. The spreadsheet column headings are described in the SCR-003.Clinical.Data.Description.txt file.
1. Improving the assessment of heart toxicity for all new drugs through translational regulatory science
Name Last modified Size Description
Parent Directory - ANNOTATORS 17-Aug-2016 13:40 29 list of annotators DOI 14-Sep-2016 16:18 19 MD5SUMS 15-Sep-2016 15:46 348 RECORDS 17-Aug-2016 14:06 395K list of record names SCR-003.Clinical.Data.Description.txt 18-Aug-2016 09:39 1.8K SCR-003.Clinical.Data.csv 18-Aug-2016 09:39 1.0M SHA1SUMS 15-Sep-2016 15:46 404 SHA256SUMS 15-Sep-2016 15:46 572 medians/ 17-Aug-2016 14:03 - raw/ 17-Aug-2016 14:05 -
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Updated Friday, 28 October 2016 at 16:58 EDT