Clinical trial NCT06029166: Subcutaneous Cardiac Monitoring of Patients With BTK Inhibitors
Official title: Electrocardiographic Changes and Rhythm Disorders Associated With BTK Inhibitors Exposure Using an Insertable Subcutaneous Cardiac Monitor: a Multicenter Cardio-Oncology Prospective Cohort
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Keywords: cardio-oncology
cardiotoxicity
hematologic malignancy
atrial fibrillation
rhythm disorders
insertable subcutaneous cardiac monitor
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
Collaborators: name: University Hospital, Marseille
name: Groupe Hospitalier Pitie-Salpetriere
name: European Georges Pompidou Hospital
name: Hôpital Necker-Enfants Malades
name: Saint Antoine University Hospital
name: Hospices Civils de Lyon
name: Centre Hospitalier Universitaire de Saint Etienne
name: Biotronik SE & Co. KG
First posted: 2023-09-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
Secondary outcomes:
measure: Electrocardiographic intervals (PR, QRS, QT) measurements on both 12-lead ECG and ISCM at baseline and with BTK inhibitors exposure.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
measure: The occurrence of bleeding events from inclusion and within 12 months.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
measure: Correlation between IRAF and multiple demographic, clinical, cardiac imaging (morphological data) and serum cardiac biomarkers.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
measure: IRAF management.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
measure: Progression-free survival of patients treated by BTK inhibitors according to the presence of IRAF.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
measure: Correlation between QT/QTc measurements performed by ISCM (BIOMONITOR IIIm®, Biotronik®) and a QT expert on 12-leads ECG.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
measure: 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.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
measure: Constitute a plasmatic biobank for futures ancillary studies.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
measure: The need for ISCM (BIOMONITOR IIIm®, Biotronik®) remove within the 12-months follow-up.
timeFrame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
Other outcomes:
Locations:
city: Caen
country: France
facility: Caen University Hospital, Department of Pharmacology
state: Normandie
Study officials:
References: