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Genetics of QT Prolongation With Antiarrhythmics (DOFEGEN)

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ClinicalTrials.gov Identifier: NCT02439658
Recruitment Status : Recruiting
First Posted : May 12, 2015
Last Update Posted : April 4, 2022
Sponsor:
Collaborators:
Mayo Clinic
The Cleveland Clinic
University of Colorado, Denver
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Christopher Newton-Cheh, MD, Massachusetts General Hospital

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.

Condition or disease Intervention/treatment
Long QT Syndrome Drug Toxicity Drug: Dofetilide and/or sotalol

Detailed 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.

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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Genetics of QT Prolongation With Antiarrhythmics
Study Start Date : January 2014
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : April 30, 2023


Group/Cohort Intervention/treatment
Dofetilide patients
Patients admitted for dofetilide initiation
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.
Other Name: Tikosyn

Sotalol patients
Patients admitted for sotalol initiation
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.
Other Name: Tikosyn




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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


Biospecimen Retention:   Samples With DNA
Blood samples for DNA extraction


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients admitted for dovetailed or sotalol initiation for clinical purposes.
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02439658


Contacts
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Contact: Christopher Newton-Cheh, MD, MPH 617-724-6158 cnewtoncheh@mgh.harvard.edu
Contact: Elizabeth Farland, BS 617-643-6328 efarland@mgh.harvard.edu

Locations
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United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Michael Rosenberg, MD       MICHAEL.A.ROSENBERG@UCDENVER.EDU   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Christopher Newton-Cheh, MD, MPH    617-643-7995    cnewtoncheh@mgh.harvard.edu   
Beth Israel Deaconess Medical Center Completed
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55902
Contact: Peter Nosewothy, MD       Noseworthy.Peter@mayo.edu   
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Khaldoun Tarakji, MD,MPH       TARAKJK@ccf.org   
Sponsors and Collaborators
Massachusetts General Hospital
Mayo Clinic
The Cleveland Clinic
University of Colorado, Denver
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Christopher Newton-Cheh, MD, MPH Massachusetts General Hospital
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Responsible Party: Christopher Newton-Cheh, MD, Overall Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02439658    
Other Study ID Numbers: 2013P001851
5R01HL143070 ( U.S. NIH Grant/Contract )
First Posted: May 12, 2015    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: March 2022
Keywords provided by Christopher Newton-Cheh, MD, Massachusetts General Hospital:
genetic research
Additional relevant MeSH terms:
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Long QT Syndrome
Drug-Related Side Effects and Adverse Reactions
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Heart Defects, Congenital
Cardiovascular Abnormalities
Congenital Abnormalities
Pathologic Processes
Chemically-Induced Disorders
Sotalol
Dofetilide
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Potassium Channel Blockers
Membrane Transport Modulators