Genetics of QT Prolongation With Antiarrhythmics
Information source: Massachusetts General Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Long QT Syndrome; Drug Toxicity
Intervention: Dofetilide and/or sotalol (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Massachusetts General Hospital Official(s) and/or principal investigator(s): Christopher Newton-Cheh, MD, MPH, Principal Investigator, Affiliation: Massachusetts General Hospital
Overall contact: Christopher Newton-Cheh, MD, MPH, Phone: 617-643-7995, Email: cnewtoncheh@mgh.harvard.edu
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.
Clinical Details
Official title: Genetics of QT Prolongation With Antiarrhythmics
Study design: Observational Model: Case Control, Time Perspective: Prospective
Primary outcome: QT interval
Secondary outcome: Successful drug initiation
Detailed description:
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 dofetilide or sotalol. One of the goals of
this study is to determine whether genetics might identify individuals at low enough genetic
risk for QT prolongation that outpatient initiation might be feasible. As an additional
safety measure of this approach might include ambulatory QT measurements, we would also like
to test the accuracy of a smart phone-based device for measuring QT interval called the
AliveCor device. The dofetilide or sotalol use will be solely determined by clinical staff
independent of the research study based on standard clinical care. The research components
of this study include only the additional collection of blood for genetic analysis,
collection of subject data on a CRF and copies of electrocardiograms performed as part of
routine clinical care. This study will be performed at Harvard hospitals including MGH,
BWH, BIDMC, all of which are eligible for participation in ceded review (MGH = primary).
Other hospitals that may participate include West Roxbury VA; local IRB approval will be
sought at each of these centers as they do not participate in the Harvard ceded review
process. Data will be collected at each individual hospital by co-investigators/site PIs
and stored locally according to IRB requirements. Copies of CRFs, ECGs and blood samples
for genetic analysis will be forwarded to MGH, which will serve as a coordinating and
analysis center (as well as a recruiting center). Data will be encoded where possible;
however, due to the impracticality of removing patient identifiers from certain data types,
such as medication lists and ECGs, some data containing patient information will be
transported and stored at MGH. Dr. Newton-Cheh will serve as overall study PI.
The investigators propose to conduct a research study to examine known and explore
potentially unknown genetic predictors of QT response in patients being admitted for
dofetilide or sotalol initiation as part of their routine clinical care. Any patient being
admitted to a participating institution for the purpose of dofetilide or sotalol initiation
will be eligible. Patients must be able to understand the risks of genetic testing, and be
willing to undergo a venipuncture for blood collection for genotyping. Exclusion criteria
include inability to provide informed consent. The investigators had planned to enroll a
goal of 500 study participants total across all participating centers, although due to lower
than expected enrollment with dofetilide alone, the investigators have included sotalol as
well to improve statistical power.
Patients will be identified by investigators based on planned admission for dofetilide or
sotalol initiation, and following explanation of the study by co-investigator, will be asked
about study participation and informed consent will be obtained. Investigators will
complete a data collection form for each patient, which will include contact information,
demographic information, clinical information, family history and pedigree, and all
electrocardiography information available (tracings, reports). Those individuals who agree
to undergo AliveCor testing will be educated in how to use the device, and a clean quality
tracing will be obtained, recorded, processed, and sent via email to the study investigation
email (QTstudies@partners. org). The time and date of the recording will be recorded on the
case report form, to allow linking with the transmission. No identifying patient
information will be entered onto the AliveCor application, and thus no identifying
information will be sent over the internet, or transmitted to the AliveCor company. No
information about mental illness will be collected. Patients will then undergo venipuncture,
and four 5mL blood samples (tubes) will be collected for genotyping. Patients will also be
consented for future re-contact about additional data, information, or samples needed for
analysis.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- All patients admitted for dovetailed or sotalol initiation for clinical purposes.
Exclusion Criteria:
- Inability to provide informed consent
- Inability to provide blood samples for DNA testing (anemia, coagulopathy)
Locations and Contacts
Christopher Newton-Cheh, MD, MPH, Phone: 617-643-7995, Email: cnewtoncheh@mgh.harvard.edu
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Recruiting Saumya Das, MD, PhD, Phone: 617-667-8800, Email: sdas@bidmc.harvard.edu
Brigham and Womens Hospital, Boston, Massachusetts 02215, United States; Recruiting Christine Albert, MD, MPH, Phone: 617-732-5500, Email: calbert@mgh.harvard.edu Ciorsti MacIntyre, MD, Phone: 617-732-5500, Email: cmacintyre@partners.org
Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting Christopher Newton-Cheh, MD, MPH, Phone: 617-643-7995, Email: cnewtoncheh@mgh.harvard.edu Michael A Rosenberg, MD, Phone: 617-726-3592, Email: marosenberg@mgh.harvard.edu
West Roxbury VA Medical Center, West Roxbury, Massachusetts 02132, United States; Recruiting Michael A Rosenberg, MD, Phone: 857-203-6840, Email: michael.rosenberg@va.gov
Additional Information
Starting date: January 2014
Last updated: May 8, 2015
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