Evidence map›Paper›PMID 25870186›Full record

Trial reportJournal of the American Heart Association2015

Comprehensive T wave morphology assessment in a randomized clinical study of dofetilide, quinidine, ranolazine, and verapamil.

Jose Vicente, Lars Johannesen, Jay W Mason, William J Crumb, Esther Pueyo, Norman Stockbridge, David G Strauss

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01873950 (A Double-Blind, Randomized, Placebo-Controlled Single-Dose, Five Period Crossover Study of the Electrocardiographic Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects), which is not on this map. Cited by 52 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 2 pooled it
14.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

NCT01873950 phase1completednot on this map

A Double-Blind, Randomized, Placebo-Controlled Single-Dose, Five Period Crossover Study of the Electrocardiographic Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects

TypeinterventionalSponsorFood and Drug Administration (FDA)Ran2013 to 2014Enrolled22ConditionsDrug-induced Surface ECG ChangesArmsRanolazine, Dofetilide, Verapamil, Quinidine sulfate, Placebo
3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.

  1. The diagnostic role of T wave morphology biomarkers in congenital and acquired long QT syndrome: A systematic review.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2023
    Pooled it
  2. Total cosine R-to-T for predicting ventricular arrhythmic and mortality outcomes: A systematic review and meta-analysis.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2018
    Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Sex-specific virtual population for the prediction and assessment of arrhythmia risk.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 · 2026
    Article
  9. Article
  10. Article
  11. Short QT intervals in African lions.Experimental physiology · 2024
    Article
  12. Review
  13. Drug-induced notched T waves.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2021
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. APL bioengineering · 2020
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 3 countries.

Jose VicenteOffice of Science and Engineering Laboratories, CDRH, US FDA, Silver Spring, MD (J.V., L.J., E.P., D.G.S.) Division of Cardiovascular and Renal Products, Office of New Drugs, CDER, US FDA, Silver Spring, MD (J.V., N.S.) BSICoS Group, Aragón Institute for Engineering Research (I3A), IIS Aragón, University of Zaragoza, Zaragoza, Spain (J.V., E.P.).
Lars JohannesenOffice of Science and Engineering Laboratories, CDRH, US FDA, Silver Spring, MD (J.V., L.J., E.P., D.G.S.) Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden (L.J., D.G.S.).
Jay W MasonSpaulding Clinical Research, West Bend, WI (J.W.M.).
William J CrumbZenas Technologies, New Orleans, Louisiana (W.J.C.).
Esther PueyoOffice of Science and Engineering Laboratories, CDRH, US FDA, Silver Spring, MD (J.V., L.J., E.P., D.G.S.) BSICoS Group, Aragón Institute for Engineering Research (I3A), IIS Aragón, University of Zaragoza, Zaragoza, Spain (J.V., E.P.) Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain (E.P.).
Norman StockbridgeDivision of Cardiovascular and Renal Products, Office of New Drugs, CDER, US FDA, Silver Spring, MD (J.V., N.S.).
David G StraussOffice of Science and Engineering Laboratories, CDRH, US FDA, Silver Spring, MD (J.V., L.J., E.P., D.G.S.) Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden (L.J., D.G.S.).
Karolinska University Hospital · SECenter for Drug Evaluation and Research · USSpaulding Clinical Research (United States) · USUnited States Food and Drug Administration · USUniversidad de Zaragoza · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCongenital long QT syndrome type 2 (abnormal hERG potassium channel) patients can develop flat, asymmetric, and notched T waves. Similar observations have been made with a limited number of hERG-blocking drugs. However, it is not known how additional calcium or late sodium block, that can decrease torsade risk, affects T wave morphology. METHODS AND

resultsTwenty-two healthy subjects received a single dose of a pure hERG blocker (dofetilide) and 3 drugs that also block calcium or sodium (quinidine, ranolazine, and verapamil) as part of a 5-period, placebo-controlled cross-over trial. At pre-dose and 15 time-points post-dose, ECGs and plasma drug concentration were assessed. Patch clamp experiments were performed to assess block of hERG, calcium (L-type) and late sodium currents for each drug. Pure hERG block (dofetilide) and strong hERG block with lesser calcium and late sodium block (quinidine) caused substantial T wave morphology changes (P<0.001). Strong late sodium current and hERG block (ranolazine) still caused T wave morphology changes (P<0.01). Strong calcium and hERG block (verapamil) did not cause T wave morphology changes. At equivalent QTc prolongation, multichannel blockers (quinidine and ranolazine) caused equal or greater T wave morphology changes compared with pure hERG block (dofetilide).

conclusionsT wave morphology changes are directly related to amount of hERG block; however, with quinidine and ranolazine, multichannel block did not prevent T wave morphology changes. A combined approach of assessing multiple ion channels, along with ECG intervals and T wave morphology may provide the greatest insight into drug-ion channel interactions and torsade de pointes risk. CLINICAL

trial registrationURL: http://clinicaltrials.gov/ Unique identifier: NCT01873950.

Indexed as

AdultCalcium Channel BlockersCross-Over StudiesElectrocardiographyERG1 Potassium ChannelEther-A-Go-Go Potassium ChannelsFemaleHeartHumansLong QT SyndromeMalePhenethylaminesQuinidineRanolazineSodium Channel BlockersSulfonamidesCalcium Channel BlockersdofetilideERG1 Potassium ChannelEther-A-Go-Go Potassium ChannelsKCNH2 protein, humanPhenethylaminesQuinidineRanolazineSodium Channel BlockersSulfonamidesVerapamilelectrocardiographyion channelslong‐QT syndromepharmacologytorsade de pointes

Identifiers

PMID25870186
PMCPMC4579946
OpenAlexW2157108097

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.