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

Atrial Fibrillation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05643235
• Other study ID #: IRB 22-0256
• Secondary ID: ERP-2021-12882
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2023
• Est. completion date: December 1, 2030

Study information

• Verified date: January 2024
• Source: Northwell Health
• Contact: Efstathia Mihelis
• Phone: 212-434-6614
• Email: emihelis[@]northwell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 1, 2030
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Atrial Fibrillation
• Chronic Lymphocytic Leukemia
• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Supraventricular Arrhythmia
• Ventricular Arrhythmias and Cardiac Arrest

Intervention

Device:
• Medtronic LINQ-2 Insertable Cardiac Monitor (ILR)
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

Locations

Country	Name	City	State
United States	Northwell (Northshore University/Long Island Jewish Hospitals)	New Hyde Park	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

References & Publications (17)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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

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. — View Citation

Ltd BU. Brukinsa Prescribing Information. 2021.

Medtronic. LINQ II LNQ22 ICM Clinician Manual. M974764A001D.

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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