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

NCT05643235 | Recruiting FDA Device

• 2 other identifiers: IRB 22-0256ERP-2021-12882
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

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)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Incidence of device detected ventricular arrhythmia (VA)

  at 18 months after start of BTK inhibitor

• BTK dose reduction or discontinuation due to device detected arrhythmia, assessed by chart review.

  up to 60 months after device implantation

• Initiation of anticoagulation for AF detected by device monitoring, assessed by chart review

  up to 60 months after device implantation

• Long term incidence of device detected ventricular arrhythmia (VA)

  up to 60 months after device implantation

Study Arms (1)

Patients initiated on Bruton tyrosine kinase inhibitors, consenting to installment of ILR

OTHER

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)

Interventions

Medtronic LINQ-2 Insertable Cardiac Monitor (ILR) DEVICE

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

Patients initiated on Bruton tyrosine kinase inhibitors, consenting to installment of ILR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Northwell (Northshore University/Long Island Jewish Hospitals)

New Hyde Park, New York, 11040, United States

RECRUITING

Related Publications (17)

• Ganatra S, Sharma A, Shah S, Chaudhry GM, Martin DT, Neilan TG, Mahmood SS, Barac A, Groarke JD, Hayek SS, Dani S, Venesy D, Patten R, Nohria A. Ibrutinib-Associated Atrial Fibrillation. JACC Clin Electrophysiol. 2018 Dec;4(12):1491-1500. doi: 10.1016/j.jacep.2018.06.004. Epub 2018 Aug 29.

  PMID: 30573111 BACKGROUND

• Baptiste F, Cautela J, Ancedy Y, Resseguier N, Aurran T, Farnault L, Escudier M, Ammar C, Gaubert M, Dolladille C, Barraud J, Peyrol M, Cohen A, Paganelli F, Alexandre J, Ederhy S, Thuny F. High incidence of atrial fibrillation in patients treated with ibrutinib. Open Heart. 2019 May 8;6(1):e001049. doi: 10.1136/openhrt-2019-001049. eCollection 2019.

  PMID: 31168393 BACKGROUND

• Guha A, Derbala MH, Zhao Q, Wiczer TE, Woyach JA, Byrd JC, Awan FT, Addison D. Ventricular Arrhythmias Following Ibrutinib Initiation for Lymphoid Malignancies. J Am Coll Cardiol. 2018 Aug 7;72(6):697-698. doi: 10.1016/j.jacc.2018.06.002. No abstract available.

  PMID: 30072003 BACKGROUND

• Lampson BL, Yu L, Glynn RJ, Barrientos JC, Jacobsen ED, Banerji V, Jones JA, Walewska R, Savage KJ, Michaud GF, Moslehi JJ, Brown JR. Ventricular arrhythmias and sudden death in patients taking ibrutinib. Blood. 2017 May 4;129(18):2581-2584. doi: 10.1182/blood-2016-10-742437. Epub 2017 Feb 21. No abstract available.

  PMID: 28223277 BACKGROUND

• Byrd JC, Hillmen P, O'Brien S, Barrientos JC, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Barr PM, Furman RR, Kipps TJ, Thornton P, Moreno C, Montillo M, Pagel JM, Burger JA, Woyach JA, Dai S, Vezan R, James DF, Brown JR. Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. Blood. 2019 May 9;133(19):2031-2042. doi: 10.1182/blood-2018-08-870238. Epub 2019 Mar 6.

  PMID: 30842083 BACKGROUND

• Tam CS, Opat S, D'Sa S, Jurczak W, Lee HP, Cull G, Owen RG, Marlton P, Wahlin BE, Sanz RG, McCarthy H, Mulligan S, Tedeschi A, Castillo JJ, Czyz J, Fernandez de Larrea C, Belada D, Libby E, Matous JV, Motta M, Siddiqi T, Tani M, Trneny M, Minnema MC, Buske C, Leblond V, Trotman J, Chan WY, Schneider J, Ro S, Cohen A, Huang J, Dimopoulos M. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenstrom macroglobulinemia: the ASPEN study. Blood. 2020 Oct 29;136(18):2038-2050. doi: 10.1182/blood.2020006844.

  PMID: 32731259 BACKGROUND

• Janssen Biotech I. Imbruciva Prescribing Information. Janssen Biotech, Inc. 2020. Accessed December 21, 2021. https://www.imbruvica.com/files/prescribing-information.pdf

  BACKGROUND

• CALQUENCE PRESCRIBING INFORMATION (AstraZeneca Pharmaceuticals LP) (2019).

  BACKGROUND

• Ltd BU. Brukinsa Prescribing Information. 2021.

  BACKGROUND

• Munir T, Brown JR, O'Brien S, Barrientos JC, Barr PM, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Kipps TJ, Moreno C, Montillo M, Burger JA, Byrd JC, Hillmen P, Dai S, Szoke A, Dean JP, Woyach JA. Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol. 2019 Dec;94(12):1353-1363. doi: 10.1002/ajh.25638. Epub 2019 Oct 13.

  PMID: 31512258 BACKGROUND

• Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, O'Brien S, Yenerel MN, Illes A, Kay N, Garcia-Marco JA, Mato A, Pinilla-Ibarz J, Seymour JF, Lepretre S, Stilgenbauer S, Robak T, Rothbaum W, Izumi R, Hamdy A, Patel P, Higgins K, Sohoni S, Jurczak W. Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial. J Clin Oncol. 2021 Nov 1;39(31):3441-3452. doi: 10.1200/JCO.21.01210. Epub 2021 Jul 26.

  PMID: 34310172 BACKGROUND

• Medtronic. LINQ II LNQ22 ICM Clinician Manual. M974764A001D.

  BACKGROUND

• Sakhi R, Theuns DAMJ, Szili-Torok T, Yap SC. Insertable cardiac monitors: current indications and devices. Expert Rev Med Devices. 2019 Jan;16(1):45-55. doi: 10.1080/17434440.2018.1557046. Epub 2018 Dec 11.

  PMID: 30522350 BACKGROUND

• Sakhi R, Huurman R, Theuns DAMJ, Schinkel AFL, Assaf A, Szili-Torok T, Roos-Hesselink JW, Michels M, Yap SC. Incremental Value of an Insertable Cardiac Monitor in Patients with Hypertrophic Cardiomyopathy with Low or Intermediate Risk for Sudden Cardiac Death. Cardiology. 2021;146(2):207-212. doi: 10.1159/000512656. Epub 2021 Jan 21.

  PMID: 33477163 BACKGROUND

• Reiffel JA, Verma A, Kowey PR, Halperin JL, Gersh BJ, Wachter R, Pouliot E, Ziegler PD; REVEAL AF Investigators. Incidence of Previously Undiagnosed Atrial Fibrillation Using Insertable Cardiac Monitors in a High-Risk Population: The REVEAL AF Study. JAMA Cardiol. 2017 Oct 1;2(10):1120-1127. doi: 10.1001/jamacardio.2017.3180.

  PMID: 28842973 BACKGROUND

• Bernstein RA, Kamel H, Granger CB, Piccini JP, Sethi PP, Katz JM, Vives CA, Ziegler PD, Franco NC, Schwamm LH; STROKE-AF Investigators. Effect of Long-term Continuous Cardiac Monitoring vs Usual Care on Detection of Atrial Fibrillation in Patients With Stroke Attributed to Large- or Small-Vessel Disease: The STROKE-AF Randomized Clinical Trial. JAMA. 2021 Jun 1;325(21):2169-2177. doi: 10.1001/jama.2021.6470.

  PMID: 34061145 BACKGROUND

• Sirichand S, Killu AM, Padmanabhan D, Hodge DO, Chamberlain AM, Brady PA, Kapa S, Noseworthy PA, Packer DL, Munger TM, Gersh BJ, McLeod CJ, Shen WK, Cha YM, Asirvatham SJ, Friedman PA, Mulpuru SK. Incidence of Idiopathic Ventricular Arrhythmias: A Population-Based Study. Circ Arrhythm Electrophysiol. 2017 Feb;10(2):e004662. doi: 10.1161/CIRCEP.116.004662.

  PMID: 28183845 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation; Heart Arrest; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Death, Sudden, Cardiac

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Death, Sudden; Death

Study Officials

• Robert S Copeland-Halperin, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

• Haisam Ismail, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Efstathia Mihelis

CONTACT

212-434-6614; emihelis@northwell.edu

Robert S Copeland-Halperin, MD

CONTACT

718-470-7330

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Cardiology

Model Details: Single arm, prospective study of implanted loop recorders (ILR) for the detection of arrhythmia in patients initiating treatment with BTK inhibitors.

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: December 8, 2022
• Study Start: January 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2030
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)