Genetics of QT Prolongation With Antiarrhythmics

NCT ID: NCT02439658

Last Updated: 2022-04-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-01-31

Study Completion Date

2023-04-30

Brief Summary

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To assess the ability of common genetic variants in aggregate to predict drug-induced QT prolongation in patients being loaded with dofetilide or sotalol.

Detailed Description

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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.

Conditions

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Long QT Syndrome Drug Toxicity

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Dofetilide patients

Patients admitted for dofetilide initiation

Dofetilide and/or sotalol

Intervention Type DRUG

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.

Sotalol patients

Patients admitted for sotalol initiation

Dofetilide and/or sotalol

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Tikosyn

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Christopher Newton-Cheh, MD

Overall Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christopher Newton-Cheh, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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University of Colorado Hospital

Aurora, Colorado, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status COMPLETED

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Christopher Newton-Cheh, MD, MPH

Role: CONTACT

617-724-6158

Elizabeth Farland, BS

Role: CONTACT

617-643-6328

Facility Contacts

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Michael Rosenberg, MD

Role: primary

Christopher Newton-Cheh, MD, MPH

Role: primary

617-643-7995

Peter Nosewothy, MD

Role: primary

Khaldoun Tarakji, MD,MPH

Role: primary

Other Identifiers

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5R01HL143070

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2013P001851

Identifier Type: -

Identifier Source: org_study_id

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