CiPA ECG Validation Study (FDA Study 3)

Version 1.0 - 13 12 2018

When referencing this material, please cite:

Vicente J, Zusterzeel R, Johannesen L, Ochoa-Jimenez R, Mason J, Sanabria C, Kemp S, Sager P, Patel V, Matta MK, Liu J, Florian J, Garnett C, Stockbridge N, Strauss DG. Assessment of Multi-Ion Channel Block in a Phase-I Randomized Study Design: Results of the CiPA Phase I ECG Biomarker Validation Study.. Clin Pharmacol Ther. doi: 10.1002/cpt.1303.

Please also include the standard citation for PhysioNet:

Goldberger AL, Amaral LAN, Glass L, Hausdorff JM, Ivanov PCh, Mark RG, Mietus JE, Moody GB, Peng C-K, Stanley HE. PhysioBank, PhysioToolkit, and PhysioNet: Components of a New Research Resource for Complex Physiologic Signals. Circulation 101(23):e215-e220 [Circulation Electronic Pages; http://circ.ahajournals.org/content/101/23/e215]; 2000 (June 13). [bib]
@article{PhysioNet,
  author    = {Goldberger, Ary L. and Amaral, Luis A. N.
               and Glass, Leon and Hausdorff, Jeffrey M.
               and Ivanov, Plamen Ch. and Mark, Roger G.
               and Mietus, Joseph E. and Moody, George B.
               and Peng, Chung-Kang and Stanley, H. Eugene},
  title     = {{PhysioBank}, {PhysioToolkit}, and {PhysioNet}:
               Components of a New Research Resource for Complex
               Physiologic Signals},
  journal   = {Circulation},
  publisher = {American Heart Association, Inc.},
  volume    = {101},
  number    = {23},
  year      = {2000},
  month     = {June},
  pages     = {e215--e220},
  doi       = {10.1161/01.CIR.101.23.e215},
  issn      = {0009-7322},
  url       = {http://circ.ahajournals.org/content/101/23/e215}
}

Introduction

ECG effects of ranolazine, verapamil, lopinavir+ritonavir, chloroquine, dofetilide, diltiazem, and dofetilide+diltiazem in a small sample size clinical study. The ECGCIPA database contains multi-channel ECG recordings of 60 subjects participating in the CiPA ECG validation study.

Experimental Method

This study assessed whether exposure response analysis of the electrocardiographic QTc and J-Tpeakc intervals in Phase 1 clinical pharmacology studies can be used to confirm that drugs that predominantly block the potassium channel encoded by the human ether-a-go-go-related gene (hERG) with approximately equipotent late sodium and/or calcium block ("balanced ion channel" drugs) do not cause J-Tpeakc prolongation and that drugs that predominantly block hERG without late sodium or L-type calcium current block ("predominant hERG" drugs) cause QTc prolongation.

This clinical study consists of 2 parts: a 50-subject parallel part (Part 1) and a 10-subject crossover part (Part 2).

More details about the rationale and study design are described in [1], which includes the study protocol and statistical analysis plan in the on-line supplement. Detailed ECG methods are described in [2]. Finally, study results are available in [3].

ClinicalTrials.gov identifier: NCT03070470 (https://clinicaltrials.gov/ct2/show/NCT03070470)

Files

The ecgcipa.zip file contains all of the WFDB ecg signal and annotation files.

References

  1. Vicente J, Zusterzeel R, Johannesen L, Mason J, Sager P, Patel V, Matta MK, Li Z, Liu J, Garnett C, Stockbridge N, Zineh I, Strauss DG. Mechanistic Model-Informed Proarrhythmic Risk Assessment of Drugs: Review of the CiPA Initiative and Design of a Prospective Clinical Validation Study. Clin Pharmacol Ther 2018 Jan; 103(1):54-66. doi: 10.1002/cpt.896
  2. Vicente J. Update on the ECG Component of the CiPA Initiative. J Electrocardiol 2018 Nov; 51(6): S98-S12. doi: 10.1016/j.jelectrocard.2018.08.003
  3. Vicente J, Zusterzeel R, Johannesen L, Ochoa-Jimenez R, Mason J, Sanabria C, Kemp S, Sager P, Patel V, Matta MK, Liu J, Florian J, Garnett C, Stockbridge N, Strauss DG. Assessment of Multi-Ion Channel Block in a Phase-I Randomized Study Design: Results of the CiPA Phase I ECG Biomarker Validation Study. Clin Pharmacol Ther. doi: 10.1002/cpt.1303
Icon  Name                    Last modified      Size  Description
[PARENTDIR] Parent Directory - [   ] ANNOTATORS 2018-12-14 17:35 80 list of annotators [   ] DOI 2019-02-11 14:29 19 [   ] RECORDS 2018-12-12 12:02 539K list of record names [TXT] addm.csv 2018-12-12 11:53 13K [TXT] adeg.csv 2018-12-12 11:53 26M [TXT] adpc.csv 2018-12-17 16:34 540K [TXT] adsl.csv 2018-12-12 11:53 11K [   ] ecgcipa_metadata.docx 2018-12-12 11:53 53K [DIR] medians/ 2018-12-12 12:05 - [DIR] raw/ 2018-12-12 12:11 -

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Updated Friday, 28 October 2016 at 16:58 EDT

PhysioNet is supported by the National Institute of General Medical Sciences (NIGMS) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB) under NIH grant number 2R01GM104987-09.