Subcutaneous Cardiac Monitoring of Patients With BTK Inhibitors (IRAF-ISCM)

Electrocardiographic Changes and Rhythm Disorders Associated With BTK Inhibitors Exposure Using an Insertable Subcutaneous Cardiac Monitor: a Multicenter Cardio-Oncology Prospective Cohort

The goal of this clinical trial is to screen all types of electrocardiographic changes and rhythm disorders in adult patients with a hematologic malignancy requiring a treatment by Bruton's tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, zanubrutinib) using an insertable subcutaneous cardiac monitor (ISCM) and occurring from inclusion and within 12 months.

This study consists of the implantation of an ISCM at inclusion and before BTK inhibitor initiation. Then patients will have medical visits every 3 months (+/- 7 days) during 12 months and a continuous cardiac telemonitoring using the ISCM.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: Insertable subcutaneous cardiac monitor (BIOMONITOR IIIm®, Biotronik®)

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joachim Alexandre, MD, PhD; Phone Number: +33 2.31.06.46.71; Email: alexandre-j@chu-caen.fr

Study Locations

• France
  • Normandie
    • Caen, Normandie, France
      • Caen University Hospital, Department of Pharmacology
      • Contact: Joachim ALEXANDRE, MDPHD; Phone Number: 0231064671; Email: alexandre-j@chu-caen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients,
• Definite diagnosis of hematologic malignancy requiring a BTK inhibition with ibrutinib, acalabrutinib or zanubrutinib,
• Expected BTK inhibitor duration estimated to be at least 12 months,
• Sinus rhythm at enrolment,
• Willing to sign patient consent form and to comply with scheduled visits, as outlined in the protocol

Exclusion Criteria:

• Age < 18 years old,
• Adults with protective measures (curatorship or tutorship) and vulnerable patients,
• Pregnant or nursing women,
• Permanent atrial fibrillation or long-standing persistent atrial fibrillation as defined by the European Society of Cardiology guidelines,
• Atrial fibrillation on the electrocardiogram at the inclusion visit,
• Previous left atrial ablation or previous maze or maze-like surgery,
• Indication for or patients with a pacemaker or implantable cardioverter-defibrillator at baseline,
• Untreated hyperthyroidism,
• Uncorrected kaliaemia disorders at the inclusion visit,
• Hemoglobin < 8 g/L at the inclusion visit,
• Thrombopenia < 50,000/mm3 at the inclusion visit,
• Active bleeding,
• Myocardial infarction < 1 month,
• Surgery < 1 month,
• Mechanical heart valve,
• Valvular heart disease requiring surgery,
• Inability to follow the required procedures of the clinical investigation plan,
• No signature of patient consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Hematologic malignancy patients requiring a treatment by Bruton's tyrosine kinase inhibitor; Consecutive adult patients with a definite diagnosis of hematologic malignancy requiring a treatment by Bruton's tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, zanubrutinib) during at least 12 months will be included to receive an insertable subcutaneous cardiac monitor (ISCM).	Device: Insertable subcutaneous cardiac monitor (BIOMONITOR IIIm®, Biotronik®); Implantation of a subcutaneous cardiac monitor (BIOMONITOR IIIm®, Biotronik®) before beginning the Bruton's tyrosine kinase inhibitor treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of any electrocardiographic changes and/or rhythm disorders from first BTK inhibitors prescription to 12 months of follow-up, symptomatic or not, detected on 12-lead ECG and/or on ISCM.	Electrocardiographic changes and/or rhythm disorders are defined by the European Society of Cardiology guidelines.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Electrocardiographic intervals (PR, QRS, QT) measurements on both 12-lead ECG and ISCM at baseline and with BTK inhibitors exposure.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
The occurrence of bleeding events from inclusion and within 12 months.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
Correlation between IRAF and multiple demographic, clinical, cardiac imaging (morphological data) and serum cardiac biomarkers.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
IRAF management.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
Progression-free survival of patients treated by BTK inhibitors according to the presence of IRAF.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
Correlation between QT/QTc measurements performed by ISCM (BIOMONITOR IIIm®, Biotronik®) and a QT expert on 12-leads ECG.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
Daily body temperature monitoring with the ISCM (BIOMONITOR IIIm®, Biotronik®) temperature sensor and will be compared with conventional body temperature measurements performed during follow-up visits.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
Constitute a plasmatic biobank for futures ancillary studies.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
The need for ISCM (BIOMONITOR IIIm®, Biotronik®) remove within the 12-months follow-up.	3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Collaborators: Hospices Civils de Lyon; Centre Hospitalier Universitaire de Saint Etienne; Saint Antoine University Hospital; Groupe Hospitalier Pitie-Salpetriere; Biotronik SE & Co. KG; University Hospital, Marseille; European Georges Pompidou Hospital; Hôpital Necker-Enfants Malades

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: August 28, 2023
• First Submitted That Met QC Criteria: September 6, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: atrial fibrillation; hematologic malignancy; cardiotoxicity; cardio-oncology; rhythm disorders; insertable subcutaneous cardiac monitor
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 22-0252

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No