Genetics of QT Prolongation With Antiarrhythmics

Long QT Syndrome Clinical Trial

— DOFEGEN  

Official title:

Genetics of QT Prolongation With Antiarrhythmics

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02439658
• Other study ID #: 2013P001851
• Secondary ID: 5R01HL143070
• Status: Recruiting
• Start date: January 2014
• Est. completion date: April 30, 2023

Study information

• Verified date: March 2022
• Source: Massachusetts General Hospital
• Contact: Christopher Newton-Cheh, MD, MPH
• Phone: 617-724-6158
• Email: cnewtoncheh[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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. 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 overseen and coordinated at MGH. Other hospitals that may participate include Mayo Clinic, Cleveland Clinic, and University of Colorado Hospital; local IRB approval will be sought at each of these centers. 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 have a goal to enroll a total of 1000 study participants across all collaborating centers.

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). Patients will then undergo venipuncture, and two 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: April 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Drug Toxicity
• Drug-Related Side Effects and Adverse Reactions
• Long QT Syndrome

Intervention

Drug:
• Dofetilide and/or sotalol
This is an observational study of patients receiving Dofetilide and/or sotalol as part of their routine clinical care. Patients receiving either of these medications will be compared with population controls for genetic analysis.

Locations

Country	Name	City	State
United States	University of Colorado Hospital	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (5)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Mayo Clinic, National Heart, Lung, and Blood Institute (NHLBI), The Cleveland Clinic, University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	QT interval	QT interval will be measured on electrocardiograms, and recorded in the case report form	QT intervals will be measured on each ECG obtained during the index hospitalization
Secondary	Successful drug initiation	This outcome will be recorded in the case report form	Patient will be followed for the duration of the hospitalization, which is on average 3 days