Evidence map›Paper›PMID 26259627›Full record

Trial reportClinical pharmacology and therapeutics2016

Late sodium current block for drug-induced long QT syndrome: Results from a prospective clinical trial.

L Johannesen, J Vicente, J W Mason, C Erato, C Sanabria, K Waite-Labott, M Hong, J Lin, P Guo, A Mutlib and 9 more

2 registry-linked trialsAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical pharmacology and therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
–field-weighted citation impact
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.

NCT02308748 phase1completednot on this map

Five Period Crossover Study of the Ability of Late Sodium or Calcium Current Block (Mexiletine, Lidocaine, or Diltiazem) to Balance the Electrocardiographic Effects of hERG Potassium Current Block (Dofetilide or Moxifloxacin)

TypeinterventionalSponsorFood and Drug Administration (FDA)Ran2014 to 2014Enrolled22ConditionsDrug-induced QT Prolongation, Pharmacokinetics, PharmacodynamicsArmsDofetilide, Mexiletine, Lidocaine, Moxifloxacin, Diltiazem
NCT05716854 phase1completednot on this mapstarted 2023, after this paper: background citation

Clinical ECG Study to Evaluate Electrophysiological Effects of Potential QT Prolonging Drugs With Novel ECG Biomarkers With Exposure-Response Analysis

TypeinterventionalSponsorFood and Drug Administration (FDA)Ran2023 to 2023Enrolled44ConditionsDrug-induced QT Prolongation, Pharmacokinetics, PharmacodynamicsArmsClarithromycin, Pimozide, Placebo (Part 1), Moxifloxacin, Cobicistat
3 · Its place in the literature

Who cites it

68 citing papers in PubMed.

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  17. Relevance of mexiletine in the era of evolving antiarrhythmic therapy of ventricular arrhythmias.Clinical research in cardiology : official journal of the German Cardiac Society · 2024
    Review
  18. Article
  19. Article
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8 more citing papers are in PubMed but not listed here.

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

19 authors.

L JohannesenCenter for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA.
J VicenteCenter for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA.
J W MasonSpaulding Clinical, West Bend, Wisconsin, USA.
C EratoSpaulding Clinical, West Bend, Wisconsin, USA.
C SanabriaSpaulding Clinical, West Bend, Wisconsin, USA.
K Waite-LabottSpaulding Clinical, West Bend, Wisconsin, USA.
M HongFrontage Laboratories, Exton, Pennsylvania, USA.
J LinFrontage Laboratories, Exton, Pennsylvania, USA.
P GuoFrontage Laboratories, Exton, Pennsylvania, USA.
A MutlibFrontage Laboratories, Exton, Pennsylvania, USA.
J WangFrontage Laboratories, Exton, Pennsylvania, USA.
W J CrumbZenas Technologies, Metairie, Louisiana, USA.
K BlinovaCenter for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA.
D ChanCenter for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA.
J StohlmanCenter for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA.
J FlorianCenter for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
M UganderCenter for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA.
N StockbridgeCenter for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
D G StraussCenter for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA.

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

Drug-induced long QT syndrome has resulted in many drugs being withdrawn from the market. At the same time, the current regulatory paradigm for screening new drugs causing long QT syndrome is preventing drugs from reaching the market, sometimes inappropriately. In this study, we report the results of a first-of-a-kind clinical trial studying late sodium (mexiletine and lidocaine) and calcium (diltiazem) current blocking drugs to counteract the effects of hERG potassium channel blocking drugs (dofetilide and moxifloxacin). We demonstrate that both mexiletine and lidocaine substantially reduce heart-rate corrected QT (QTc) prolongation from dofetilide by 20 ms. Furthermore, all QTc shortening occurs in the heart-rate corrected J-Tpeak (J-Tpeak c) interval, the biomarker we identified as a sign of late sodium current block. This clinical trial demonstrates that late sodium blocking drugs can substantially reduce QTc prolongation from hERG potassium channel block and assessment of J-Tpeak c may add value beyond only assessing QTc.

Indexed as

AdultAnti-Arrhythmia AgentsCalcium Channel BlockersCross-Over StudiesDiltiazemDrug Therapy, CombinationElectrocardiographyEther-A-Go-Go Potassium ChannelsFemaleFluoroquinolonesHeart RateHumansLidocaineLong QT SyndromeMaleMexiletineAnti-Arrhythmia AgentsCalcium Channel BlockersDiltiazemdofetilideEther-A-Go-Go Potassium ChannelsFluoroquinolonesLidocaineMexiletineMoxifloxacinPhenethylaminesSodium Channel BlockersSulfonamides

Identifiers

PMID26259627
PMCPMC5421403

What OpenQuestion holds

Textmetadata
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.