xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06029166</url>
    </required_header>
    <id_info>
      <org_study_id>22-0252</org_study_id>
      <nct_id>NCT06029166</nct_id>
    </id_info>
    <brief_title>Subcutaneous Cardiac Monitoring of Patients With BTK Inhibitors</brief_title>
    <acronym>IRAF-ISCM</acronym>
    <official_title>Electrocardiographic Changes and Rhythm Disorders Associated With BTK Inhibitors Exposure Using an Insertable Subcutaneous Cardiac Monitor: a Multicenter Cardio-Oncology Prospective Cohort</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Caen</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University Hospital, Marseille</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Groupe Hospitalier Pitie-Salpetriere</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>European Georges Pompidou Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Hôpital Necker-Enfants Malades</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Saint Antoine University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Hospices Civils de Lyon</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Centre Hospitalier Universitaire de Saint Etienne</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Biotronik SE &amp; Co. KG</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University Hospital, Caen</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to screen all types of electrocardiographic changes and&#xD;
        rhythm disorders in adult patients with a hematologic malignancy requiring a treatment by&#xD;
        Bruton's tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, zanubrutinib) using an&#xD;
        insertable subcutaneous cardiac monitor (ISCM) and occurring from inclusion and within 12&#xD;
        months.&#xD;
  &#xD;
        This study consists of the implantation of an ISCM at inclusion and before BTK inhibitor&#xD;
        initiation. Then patients will have medical visits every 3 months (+/- 7 days) during 12&#xD;
        months and a continuous cardiac telemonitoring using the ISCM.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2026</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <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.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
      <description>Electrocardiographic changes and/or rhythm disorders are defined by the European Society of Cardiology guidelines.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Electrocardiographic intervals (PR, QRS, QT) measurements on both 12-lead ECG and ISCM at baseline and with BTK inhibitors exposure.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The occurrence of bleeding events from inclusion and within 12 months.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation between IRAF and multiple demographic, clinical, cardiac imaging (morphological data) and serum cardiac biomarkers.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IRAF management.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival of patients treated by BTK inhibitors according to the presence of IRAF.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation between QT/QTc measurements performed by ISCM (BIOMONITOR IIIm®, Biotronik®) and a QT expert on 12-leads ECG.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <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.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Constitute a plasmatic biobank for futures ancillary studies.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The need for ISCM (BIOMONITOR IIIm®, Biotronik®) remove within the 12-months follow-up.</measure>
      <time_frame>3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Atrial Fibrillation</condition>
    <arm_group>
      <arm_group_label>Hematologic malignancy patients requiring a treatment by Bruton's tyrosine kinase inhibitor</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>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).</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Insertable subcutaneous cardiac monitor (BIOMONITOR IIIm®, Biotronik®)</intervention_name>
      <description>Implantation of a subcutaneous cardiac monitor (BIOMONITOR IIIm®, Biotronik®) before beginning the Bruton's tyrosine kinase inhibitor treatment.</description>
      <arm_group_label>Hematologic malignancy patients requiring a treatment by Bruton's tyrosine kinase inhibitor</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adult patients,&#xD;
  &#xD;
            -  Definite diagnosis of hematologic malignancy requiring a BTK inhibition with&#xD;
               ibrutinib, acalabrutinib or zanubrutinib,&#xD;
  &#xD;
            -  Expected BTK inhibitor duration estimated to be at least 12 months,&#xD;
  &#xD;
            -  Sinus rhythm at enrolment,&#xD;
  &#xD;
            -  Willing to sign patient consent form and to comply with scheduled visits, as outlined&#xD;
               in the protocol&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Age &lt; 18 years old,&#xD;
  &#xD;
            -  Adults with protective measures (curatorship or tutorship) and vulnerable patients,&#xD;
  &#xD;
            -  Pregnant or nursing women,&#xD;
  &#xD;
            -  Permanent atrial fibrillation or long-standing persistent atrial fibrillation as&#xD;
               defined by the European Society of Cardiology guidelines,&#xD;
  &#xD;
            -  Atrial fibrillation on the electrocardiogram at the inclusion visit,&#xD;
  &#xD;
            -  Previous left atrial ablation or previous maze or maze-like surgery,&#xD;
  &#xD;
            -  Indication for or patients with a pacemaker or implantable cardioverter-defibrillator&#xD;
               at baseline,&#xD;
  &#xD;
            -  Untreated hyperthyroidism,&#xD;
  &#xD;
            -  Uncorrected kaliaemia disorders at the inclusion visit,&#xD;
  &#xD;
            -  Hemoglobin &lt; 8 g/L at the inclusion visit,&#xD;
  &#xD;
            -  Thrombopenia &lt; 50,000/mm3 at the inclusion visit,&#xD;
  &#xD;
            -  Active bleeding,&#xD;
  &#xD;
            -  Myocardial infarction &lt; 1 month,&#xD;
  &#xD;
            -  Surgery &lt; 1 month,&#xD;
  &#xD;
            -  Mechanical heart valve,&#xD;
  &#xD;
            -  Valvular heart disease requiring surgery,&#xD;
  &#xD;
            -  Inability to follow the required procedures of the clinical investigation plan,&#xD;
  &#xD;
            -  No signature of patient consent form.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Joachim Alexandre, MD, PhD</last_name>
      <phone>+33 2.31.06.46.71</phone>
      <email>alexandre-j@chu-caen.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>Caen University Hospital, Department of Pharmacology</name>
        <address>
          <city>Caen</city>
          <state>Normandie</state>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Joachim ALEXANDRE, MDPHD</last_name>
        <phone>0231064671</phone>
        <email>alexandre-j@chu-caen.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>cardio-oncology</keyword>
    <keyword>cardiotoxicity</keyword>
    <keyword>hematologic malignancy</keyword>
    <keyword>atrial fibrillation</keyword>
    <keyword>rhythm disorders</keyword>
    <keyword>insertable subcutaneous cardiac monitor</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Atrial Fibrillation</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06029166
  org study id: 22-0252
  nct id: NCT06029166
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  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.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Diagnostic
  masking: None (Open Label)
  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.
  time frame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
  description: Electrocardiographic changes and/or rhythm disorders are defined by the European Society of Cardiology guidelines.
  measure: Electrocardiographic intervals (PR, QRS, QT) measurements on both 12-lead ECG and ISCM at baseline and with BTK inhibitors exposure.
  time frame: 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.
  time frame: 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.
  time frame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
  measure: IRAF management.
  time frame: 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.
  time frame: 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.
  time frame: 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.
  time frame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
  measure: Constitute a plasmatic biobank for futures ancillary studies.
  time frame: 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.
  time frame: 3, 6, 9 and 12 months after introduction of ibrutinib therapy (+/- 7 days)
  arm group label: Hematologic malignancy patients requiring a treatment by Bruton's tyrosine kinase inhibitor
  arm group type: Other
  description: 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).
  intervention type: Device
  intervention name: Insertable subcutaneous cardiac monitor (BIOMONITOR IIIm®, Biotronik®)
  description: Implantation of a subcutaneous cardiac monitor (BIOMONITOR IIIm®, Biotronik®) before beginning the Bruton's tyrosine kinase inhibitor treatment.
  arm group label: Hematologic malignancy patients requiring a treatment by Bruton's tyrosine kinase inhibitor
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Joachim Alexandre, MD, PhD
  phone: +33 2.31.06.46.71
  email: alexandre-j@chu-caen.fr
  facility: 
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Atrial Fibrillation
  sharing ipd: Undecided