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

NCT ID: NCT05724121

Last Updated: 2025-11-10

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

RECRUITING

Total Enrollment

135 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-03-01

Study Completion Date

2027-04-08

Brief Summary

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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.

...

Detailed Description

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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

Conditions

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

Keywords

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SUDDEN CARDIAC DEATH Chronic Lymphocytic Leukemia (CLL) Ibrutinib Treatment Atrial Fibrillation/Flutter Ventricular Arrhythmias Natural History

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort A

includes all patients prior to starting therapy with a BTKi

No interventions assigned to this group

Cohort B

includes all patients already on therapy with a BTKi

No interventions assigned to this group

Cohort C

includes all patients prior to starting therapy with venetoclax

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

110 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christine E Gruessner, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ingrid C Frey

Role: CONTACT

Phone: (301) 312-0765

Email: [email protected]

Christine E Gruessner, M.D.

Role: CONTACT

Phone: (240) 550-6022

Email: [email protected]

Facility Contacts

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NIH Clinical Center Office of Patient Recruitment (OPR)

Role: primary

Related Links

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Other Identifiers

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000923-H

Identifier Type: -

Identifier Source: secondary_id

10000923

Identifier Type: -

Identifier Source: org_study_id