Recruiting

NCT Number: NCT05724121

Observational Study of Cardiac Arrhythmias During Treatment With BTK Inhibitors or Venetoclax

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.

...

Recruiting

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Key information

Conditions

Chronic Lymphocytic Leukemia (CLL) Arrhythmias, Cardiac Atrial Fibrillation Cardiac Arrhythmias Cardiovascular Diseases Chronic Disease Death Death, Sudden Death, Sudden, Cardiac Disease Attributes Heart Arrest Heart Diseases Hematologic Diseases Hematologic Malignancies Hematologic Neoplasms Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoma Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Mantle Cell Lymphoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Sudden Cardiac Death Waldenstr(SqrRoot)(Delta)m s Macroglobulinemia

Age range

18 year–110 year

Sex eligibility

All sexes

Study type

Observational

Primary location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location status: Recruiting

Location contact

NIH Clinical Center Office of Patient Recruitment (OPR)

CONTACT

[email protected]

800-411-1222 ext. TTY dial 711

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

INCLUSION CRITERIA:

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

Currently receiving or planning to receive a BTKi or venetoclax.
Male or female, aged 18 or older
Stated willingness to comply with all study procedures and availability for the duration of the study
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:

Any acute cardiac condition including myocardial infarction or decompensated heart failure within the past 3 months
Pregnancy or lactation- use of BTK inhibitors is contraindicated in pregnant or nursing individuals.

Treatment and study plan

Primary outcomes

arrhythmogenic cardiac effects of BTKi and sudden death within the first 12 months of BTKi therapy

Time frame: 12 months
- 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 outcomes

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

Study contacts

Contact information is provided by the study sponsor or research team.

Christine E Gruessner, M.D.

CONTACT

[email protected]

(240) 550-6022

Ingrid C Frey

CONTACT

[email protected]

(301) 402-0797

Sponsors and collaborators

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Nih

Registry information

Important dates

Study start: 2023
Primary completion: 2027
Study completion: 2027
First posted: Feb 13, 2023
Registry last updated: Jul 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed