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Trial record 2 of 2 for:    IMAGE BTK
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Observational Study of Cardiac Arrhythmias During Treatment With BTK Inhibitors or Venetoclax

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ClinicalTrials.gov Identifier: NCT05724121
Recruitment Status : Recruiting
First Posted : February 13, 2023
Last Update Posted : April 5, 2024
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Study Description
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

Background:

Bruton s tyrosine kinase inhibitors (BTKi) are used to treat a form of leukemia. But taking BTKi can also increase a person s risk of developing an abnormal heart rhythm. This can cause sudden death. In this natural history study, researchers want to learn how BTKi affects the heart.

Objective:

To identify and monitor the effects of BTKi on the heart.

Eligibility:

People aged 18 and older currently receiving or planning to receive BTKi or venetoclax.

Design:

Participants who have not yet started BTKi will have 2 required clinic visits: 1 before they start taking BTKi, and 1 about 6 months later. Participants who are already taking BTKi will have 1 required visit.

Participants will undergo multiple tests:

A physical exam, including collection of blood and saliva.

A test that measures heart activity via stickers placed on the chest.

A test that uses sound waves to capture images of the heart.

An exercise stress test that monitors heart activity and blood pressure while the participant works on a treadmill or stationary bike. Sound wave images of the heart may also be taken while the participant exercises.

Stress magnetic resonance imaging (MRI) may be done in place of an exercise test. Participants will lie on a table that slides into a tube. They will be given drugs to stress the heart while images are taken.

Participants may wear a device to monitor their heart at home.

Participants may have repeat visits if they develop heart symptoms or if they need to stop taking BTKi. They will have follow-up phone calls each year for up to 3 years.


Condition or disease
Chronic Lymphocytic Leukemia (CLL) Waldenstr(SqrRoot)(Delta)m s Macroglobulinemia Mantle Cell Lymphoma Sudden Cardiac Death Cardiac Arrhythmias Hematologic Malignancies

Detailed Description:

Study Description:

Pharmacologic therapy with BTK inhibitors (BTKi) is associated with an increased risk of cardiac arrhythmias which can lead to sudden death. There is currently no standard for cardiac screening or monitoring patients on BTKi. We hypothesize that thorough and routine comprehensive cardiac evaluations prior to starting therapy with BTKi and repeated during therapy with BTKi will result in earlier identification of cardiac arrhythmias with the goal of minimizing associated morbidity and mortality. In addition, venetoclax, a different standard therapy for chronic lymphocytic leukemia, has not been associated with increased cardiac adverse events and could serve as a control group.

Objectives:

Primary objective: Identify, monitor, and analyze the arrhythmogenic effects of BTKi as well as sudden death

Secondary objective: Assess the utility of different cardiac tests for identifying and monitoring cardiac arrhythmias in patients receiving BTKi or venetoclax

Exploratory objective: To examine the relationship between the development of cardiac arrhythmias in patients on BTKi as it relates to other variables

Endpoints:

Primary endpoint:

-A composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting a BTKi (Cohort A) and in patients already receiving BTKi (Cohort B).

Secondary endpoints:

  • Detection of arrhythmias on devices (rest/stress EKG, ambulatory EKG monitor, KardiaMobile)
  • Arrhythmia (treatment emergent or worsening) in patients on BTKi
  • Sudden death in patients on BTKi
  • A composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting venetoclax
  • Difference in cardiac arrhythmias and sudden death between different BTKi groups (e.g., ibrutinib vs. non-ibrutinib group)
  • Difference in cardiac arrhythmias and sudden death between BTKi and venetoclax groups

Exploratory endpoints:

  • Pharmacokinetic levels of BTKi
  • Duration of BTKi exposure
  • Cumulative BTKi dose
  • Genetic variants
  • Cardiac structural remodeling
  • Medical comorbidities
  • Concomitant medications
  • Substance use
  • Identify risk factors or biomarkers for arrhythmia
Study Design
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Study Type : Observational
Estimated Enrollment : 135 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Observational Study of Cardiac Arrhythmias During Treatment With BTK Inhibitors or Venetoclax
Actual Study Start Date : March 1, 2023
Estimated Primary Completion Date : April 8, 2027
Estimated Study Completion Date : April 8, 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Venetoclax

Groups and Cohorts
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Group/Cohort
Cohort A
includes all patients prior to starting therapy with a BTKi
Cohort B
includes all patients already on therapy with a BTKi
Cohort C
includes all patients prior to starting therapy with venetoclax


Outcome Measures
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Primary Outcome Measures :
  1. arrhythmogenic cardiac effects of BTKi and sudden death within the first 12 months of BTKi therapy [ Time Frame: 12 months ]
    1. Clinically significant cardiac arrhythmias while on a BTKi (treatment emergent in those without a history of arrhythmias and worsening of arrhythmia for those with an arrhythmia at the time of enrollment testing) within 12 months. For Cohort A, if a patient has an arrhythmia at the time of baseline testing, only worsening or new arrhythmias will be called an event. For Cohort B, all arrhythmias will be called an event. 2. Sudden death


Secondary Outcome Measures :
  1. tests for identifying and monitoring cardiac arrhythmias in patients receiving BTKi [ Time Frame: 36 months ]
    -Detection of arrhythmias on devices (rest EKG, stress EKG, ambulatory EKG monitor, KardiaMobile) -Clinically significant and other arrhythmias (treatment emergent or worsening) in patients on BTKi and on venetoclax -Sudden death -Composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting venetoclax -Differences in cardiac arrhythmias and sudden death within BTKi (e.g., ibrutinib vs. non-ibrutinib group) -Differences in cardiac arrhythmias and sudden death between patients on BTKi and venetoclax


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 110 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Sample size of 135 subjects including men and women over 18 years old followed at the NIH Clinical Center who are either about to start a BTKi (Cohort A) or venetoclax (Cohort C) as well as those already taking BTKi (Cohort B)
Criteria
  • INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all of the following criteria:

  1. Currently receiving or planning to receive a BTKi or venetoclax.
  2. Male or female, aged 18 or older
  3. Stated willingness to comply with all study procedures and availability for the duration of the study
  4. Ability of subject to understand and the willingness to sign a written informed consent document

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Any acute cardiac condition including myocardial infarction or decompensated heart failure within the past 3 months
  2. Pregnancy or lactation- use of BTK inhibitors is contraindicated in pregnant or nursing individuals.
Contacts and Locations
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT05724121


Contacts
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Contact: Shellin Jose (301) 529-7119 shellin.jose@nih.gov
Contact: Christine E Gruessner, M.D. (240) 550-6022 christine.gruessner@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: NIH Clinical Center Office of Patient Recruitment (OPR)    800-411-1222 ext TTY dial 711    ccopr@nih.gov   
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Christine E Gruessner, M.D. National Heart, Lung, and Blood Institute (NHLBI)
More Information
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Additional Information:

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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT05724121    
Other Study ID Numbers: 10000923
000923-H
First Posted: February 13, 2023    Key Record Dates
Last Update Posted: April 5, 2024
Last Verified: April 1, 2024

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
SUDDEN CARDIAC DEATH
Chronic Lymphocytic Leukemia (CLL)
Ibrutinib Treatment
 Atrial Fibrillation/Flutter
Ventricular Arrhythmias
Natural History
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Hematologic Neoplasms
Arrhythmias, Cardiac
Death, Sudden, Cardiac
Death
Leukemia
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes
Lymphoma, Non-Hodgkin
Lymphoma
Heart Diseases
Cardiovascular Diseases
Neoplasms by Site
Heart Arrest
Death, Sudden