Implanted Loop Recorders for Detection and Management of Arrhythmia With Bruton Tyrosine Kinase Inhibitors

Study Overview
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Brief Summary
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This study will enroll patients initiating Bruton Tyrosine Kinase (BTK) inhibitors without history of documented arrhythmia while on therapy using the Medtronic LINQ-2 insertable cardiac monitor (ILR). The incidence of new onset atrial fibrillation (AF) and other arrhythmia will be determined. Actions taken in response to device detected arrhythmia will be recorded.

Detailed Description
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This single arm, prospective non-blinded study will enroll 50 patients initiating treatment with BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib or pirtobrutinib) without documented arrhythmia prior to starting BTK inhibitor therapy, without contraindications to an implanted loop recorder (ILR). They will be offered the option of monitoring arrhythmias using the Medtronic LINQ-2 insertable cardiac monitor (ILR). Monitoring data will be collected prospectively until the patient withdraws consent, the device is removed, or up to 60 months. Investigators hope to obtain information on arrhythmia incidence including AF, ventricular arrhythmia (VA), and actions taken in response to awareness of such episodes.

Official Title
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Implanted Loop Recorders (ILR) for the Detection and Management of Arrhythmia in Patients Treated With Bruton Tyrosine Kinase (BTK) Inhibitors

Conditions
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Atrial Fibrillation, Supraventricular Arrhythmia, Ventricular Arrhythmias and Cardiac Arrest, Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Intervention / Treatment
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* Device: Medtronic LINQ-2 Insertable Cardiac Monitor (ILR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18yo Willing to sign and date consent form, Willing to be remotely monitored Initiating BTK inhibitor for approved condition (i.e. CLL, Waldenstrom's, etc) Willing to have Medtronic cardiac monitor inserted to allow at minimum 24 hours continuous monitoring prior to initiating BTK inhibitor Exclusion Criteria: Documented AF/VA in past 12 months Cerebral Vascular Accident (CVA) or Transient Ischemic Attack (TIA) in past year Has current implanted pulse generator, defibrillator, pacemaker, or resynchronization device heart surgery within past 90 days Myocardial Infarction within past 90 days Patient is taking an anti-arrhythmic or anticoagulant has concomitant condition that precludes safe participation in study (substance abuse, etc) Enrollment in separate study that could confound results of this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm, prospective study of implanted loop recorders (ILR) for the detection of arrhythmia in patients initiating treatment with BTK inhibitors.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patients initiated on Bruton tyrosine kinase inhibitors, consenting to installment of ILR<br>Patients free of documented arrhythmia initiating treatment with a BTK inhibitor who consent to monitoring using the Medtronic LINQ-2 implanted cardiac monitoring device (ILR) prior to initiating BTK inhibitor therapy. | Device: Medtronic LINQ-2 Insertable Cardiac Monitor (ILR)<br>* Patients initiating BTK inhibitors will be offered the option of monitoring using the Medtronic Insertable Cardiac Monitor (ILR). The device will be implanted by a certified and credentialed electrophysiologist to enable monitoring to begin at least 24 hours prior to the first administration of the BTK inhibitor. Monitoring data will be collected prospectively until the patient withdraws consent, the device is removed, or up to 60 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of device detected atrial fibrillation (AF) | Incidence of AF lasting 6 or more minutes at 18 months: each arrhythmic episode detected by the patient's device will be reviewed to determine if it is 1) an actual AF episode, and 2) is at least 6 minutes in duration. | at 18 months after start of BTK inhibitor | 
| Long term Incidence of device detected AF | Incidence of AF lasting 6 or more minutes up to 60 months: each arrhythmic episode detected by the patient's device will be reviewed to determine if it is 1) an actual AF episode, and 2) is at least 6 minutes in duration. | up to 60 months after device implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of device detected ventricular arrhythmia (VA) | Incidence of VA is defined as follows: greater than or equal to 3 sequential wide complex beats arising from the ventricles, rate > 100 beats per minute at 18 months after start of BTK inhibitor therapy. | at 18 months after start of BTK inhibitor | 
| BTK dose reduction or discontinuation due to device detected arrhythmia, assessed by chart review. | Clinical actions including BTK dose reduction, interruption, discontinuation, or change in oncologic treatment by treating oncologist because of device detected arrhythmia. | up to 60 months after device implantation | 
| Initiation of anticoagulation for AF detected by device monitoring, assessed by chart review | Prescription of an approved anticoagulant drug (apixaban, dabigatran, rivaroxaban, edoxaban, warfarin, aspirin) for prevention of stroke/systemic embolism based on AF detected by ILR | up to 60 months after device implantation | 
| Long term incidence of device detected ventricular arrhythmia (VA) | Incidence of VA is defined as follows: greater than or equal to 3 sequential wide complex beats arising from the ventricles, rate > 100 beats per minute up to 60 months after device implant. | up to 60 months after device implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bruton tyrosine kinase (BTK), Chronic Lymphocytic Leukemia (CLL), Mantle Cell Lymphoma, Waldenstrom's macroglobulinemia, atrial fibrillation (AF), ventricular arrhythmia (VA), sudden cardiac death, ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib, Implanted Loop Recorder/Implanted Cardiac Monitor (ILR)