Clinical trial NCT05724121: Observational Study of Cardiac Arrhythmias During Treatment With BTK Inhibitors or Venetoclax
Official title: Observational Study of Cardiac Arrhythmias During Treatment With BTK Inhibitors or Venetoclax
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Lymphocytic Leukemia (CLL)
Waldenstr(SqrRoot)(Delta)m s Macroglobulinemia
Mantle Cell Lymphoma
Sudden Cardiac Death
Cardiac Arrhythmias
Hematologic Malignancies
Keywords: SUDDEN CARDIAC DEATH
Chronic Lymphocytic Leukemia (CLL)
Ibrutinib Treatment
Atrial Fibrillation/Flutter
Ventricular Arrhythmias
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2023-02-13
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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)

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.

...

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

Eligibility 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.

Primary outcomes:
measure: arrhythmogenic cardiac effects of BTKi and sudden death within the first 12 months of BTKi therapy
timeFrame: 12 months
Secondary outcomes:
measure: tests for identifying and monitoring cardiac arrhythmias in patients receiving BTKi
timeFrame: 36 months
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Christine E Gruessner, M.D.
role: PRINCIPAL_INVESTIGATOR
References: