A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes (BA-TdP)

November 22, 2021 updated by: Christopher Newton-Cheh, MD, Massachusetts General Hospital
This is a registry to examine genetic and clinical predictors of torsade de pointes events.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

BACKGROUND AND SIGNIFICANCE Drug-induced long QT syndrome (LQTS), and the subsequent fatal arrhythmia torsade de pointes (TdP), is an important side effect associated with the 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.

Although common genetic variants associated with sudden cardiac death have been identified, studies specifically identifying variants associated with drug-induced LQTS and TdP are limited. Smaller studies have suggested that variants of genes associated with QT interval duration in the population in general are also associated with the risk of drug-induced QT prolongation and TdP, but larger studies are needed. Moreover, an improved ability to predict the causes of TdP requires a careful search for clinical factors associated with TdP compared to controls.

RESEARCH DESIGN AND METHODS

A. Study Design and Enrollment: We propose to conduct a multi-center research study to examine known and explore potentially unknown genetic and clinical predictors of torsade de pointes (TdP) also known as acquired long QT syndrome (LQTS) through creation of a registry. Any patient with a documented history of a torsade de pointes (TdP) event 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. We plan to enroll a total of 200 study participants total across all participating centers. Massachusetts General Hospital will be the coordinating center of this multi-center study of medical institutions within the greater Boston and New England area. In a substudy to take place at MGH, subjects will be invited to have a punch biopsy of the skin to allow creation of inducible pluripotent stem cells that can be differentiated into cardiomyocytes for further characterization of the repolarization phenotype.

B. Study Procedures: We will screen patients for enrollment including both retrospective (event prior to the start of the study) and prospective (event following the start of the study) components. Patients will be identified by investigators based on clinical characteristics, and following explanation of the study by co-investigators, will be asked about participation either during routine scheduled follow-up (for retrospective cases) or at the sentinel event. 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 (12-lead ECGs, rhythm strips and summary reports). No information about mental illness will be collected. Patients will then undergo venipuncture, and four 5mL blood samples will be collected for genotyping and plasma analysis. For patients who are willing, a 3mm punch biopsy from the shoulder, upper thigh, small of the back, or buttock (subject's choice) will be obtained for fibroblast culture. Patients who are recruited at non-MGH sites will have a visit to MGH scheduled in order to obtain the skin biopsy. Induced pluripotent stem cells will be made from the fibroblast cultures and differentiated to cardiomyocytes in order to assess the cellular phenotype. Patients will also be consented for future re-contact about additional data, information, or samples needed for analysis. All clinical information and samples (including DNA and blood) collected at participating centers will be transferred to Dr. Newton-Cheh at MGH for storage and analysis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02118
        • Boston University Medical Center
      • West Roxbury, Massachusetts, United States, 02132
        • West Roxbury VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Any patient in which informed consent can be obtained, with a history of torsade de points (see below designation).

Description

For simplicity, we will plan to include all possible cases of TdP meeting criteria (see below) into the registry.

Exclusion criteria include:

  1. age <18 years old
  2. inability to obtain informed consent from the patient or a family member
  3. no exclusion on the basis of race or gender.

Inclusion criteria include:

torsade de pointes clinical syndrome according to one of the following three clinical criteria:

  1. Definite TdP: At least 3 beats of polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) on a 12-lead ECG or rhythm strip with documented QTc > 450 ms in men or QTc > 470 in women (excluding patients with conduction block or AF at baseline, see below) prior to arrhythmic event.
  2. Probable TdP: At least 3 beats of polymorphic VT or VF on a 12-lead ECG or rhythm strip with QTc > 450ms (men) or 470ms (women) after the event, or polymorphic VT or VF episode not meeting criteria for 'definite TdP' but determined by the adjudicating physician to be likely TdP. For patients having a cardiac arrest, at least 1 hour after restoration of normal rhythm or after secondary hypoxia or electrolyte abnormalities have been ruled out (confounders of QT prolongation often seen post-arrest47) will be required.
  3. Possible TdP: Unexplained syncope in a patient presenting with QTc > 450ms (men) or 470ms (women).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Torsade de pointes arrhythmia events
Time Frame: Participants will be followed for the time to obtain consent, clinical information and biospecimens (typically < 1 day)
  1. Definite TdP: At least 3 beats of polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) on a 12-lead ECG or rhythm strip with documented QTc > 450 ms in men or QTc > 470 in women (excluding patients with conduction block or AF at baseline, see below) prior to arrhythmic event.
  2. Probable TdP: At least 3 beats of polymorphic VT or VF on a 12-lead ECG or rhythm strip with QTc > 450ms (men) or 470ms (women) after the event, or polymorphic VT or VF episode not meeting criteria for 'definite TdP' but determined by the adjudicating physician to be likely TdP. For patients having a cardiac arrest, at least 1 hour after restoration of normal rhythm or after secondary hypoxia or electrolyte abnormalities have been ruled out (confounders of QT prolongation often seen post-arrest47) will be required.
  3. Possible TdP: Unexplained syncope in a patient presenting with QTc > 450ms (men) or 470ms (women).
Participants will be followed for the time to obtain consent, clinical information and biospecimens (typically < 1 day)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Boston University
Mayo Clinic
Beth Israel Deaconess Medical Center
The Cleveland Clinic
Brigham and Women's Hospital
US Department of Veterans Affairs

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christopher Newton-Cheh, MD, MPH, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 26, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 26, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 12, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 3, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 22, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2013P001531

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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