Clinical Trial: Genetics of QT Prolongation With Antiarrhythmics

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Genetics of QT Prolongation With Antiarrhythmics

Brief Summary: To assess the ability of common genetic variants in aggregate to predict drug-induced QT prolongation in patients being loaded with dofetilide or sotalol, and validate the feasibility of using a smartphone device for measuring QT interval.

Detailed Summary:

Drug-induced long QT syndrome (LQTS), and the subsequent fatal arrhythmia torsade de pointes (TdP), is a major concern with use of a number of medications. Prolongation of the QT interval is the most common cause of withdrawal of medications already on the market, and despite the relatively rarity with non-cardiovascular drugs, the public health impact is magnified by the fact that drug-induced TdP can occur with medications used for benign conditions, such as allergic rhinitis. The QT interval is heritable, and a number of common genetic variants have been associated with QT interval in large population studies.

Dofetilide is a commonly used anti-arrhythmic medication known to be associated with drug-induced LQTS to such a degree that the Federal Drug Administration requires a mandatory 3 day hospitalization with initiation to screen for QT prolongation. Sotalol is also a commonly-used anti-arrhythmic medication that is associated with drug-induced LQTS and requires a 3 day hospitalization for initiation, although it does not have an FDA-specified initiation protocol like dofetilide. Although certain clinical predictors have been associated with prolongation of QT with dofetilide or sotalol, there is limited information about genetic predictors of QT prolongation. As identification of such genetic predictors could help to identify potentially toxic responses in this and other medications, we plan to examine genetic predictors of QT interval on the QT prolongation with dofetilide or sotalol. In addition, to assess the feasibility (and safety) of using genetic-guided outpatient initiation, we plan to study the accuracy of the AliveCor device for measuring QT interval in select patients.

STUDY OVERVIEW: This study is a multi-center study attempting to identify genetic and other factors that influence QT interval response to
Sponsor: Massachusetts General Hospital

Current Primary Outcome: QT interval [ Time Frame: QT intervals will be measured on each ECG obtained during the index hospitalization ]

QT interval will be measured on electrocardiograms, and recorded in the case report form


Original Primary Outcome: Same as current

Current Secondary Outcome: Successful drug initiation [ Time Frame: Patient will be followed for the duration of the hospitalization, which is on average 3 days ]

This outcome will be recorded in the case report form


Original Secondary Outcome: Same as current

Information By: Massachusetts General Hospital

Dates:
Date Received: May 5, 2015
Date Started: January 2014
Date Completion: January 2019
Last Updated: March 27, 2016
Last Verified: March 2016