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/NCT06038708</url>
    </required_header>
    <id_info>
      <org_study_id>BA117</org_study_id>
      <nct_id>NCT06038708</nct_id>
    </id_info>
    <brief_title>Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial</brief_title>
    <acronym>BIO|Sync-HUTT</acronym>
    <official_title>BIO|Sync-HUTT: Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Biotronik SE &amp; Co. KG</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Biotronik SE &amp; Co. KG</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to explore changes in patients' hemodynamic parameters during&#xD;
        the Head-Up Tilt Test (&quot;HUTT&quot;) and their timing with respect to onset of the Closed Loop&#xD;
        Stimulation (CLS) pacing. This study aims to add knowledge to better understand the&#xD;
        mechanisms underlying recurrent syncopal events and optimal pacing programming.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The 2021 European Society of Cardiology guidelines recommend cardiac pacing in patients aged&#xD;
        &gt;40 years with tilt-induced asystolic reflex syncope (class I, level of evidence A). The&#xD;
        recommendation relies on recent results from the multicentre, randomised, double-blinded,&#xD;
        parallel-design BIOSync trial (NCT02324920). The BIOSync study provided evidence of benefit&#xD;
        of dual chamber pacing in patients with tilt-induced reflex syncope and confirmed the role of&#xD;
        Head-up Tilt Table (HUTT) test as a diagnostic method for cardiac pacing in reflex syncope.&#xD;
        The Closed Loop Stimulation (CLS) is able to measure changes in intracardiac impedance during&#xD;
        the systolic phase of each cardiac cycle which are strictly correlated to the increased heart&#xD;
        rate and right ventricular contraction speed which are usually present during the pre-syncope&#xD;
        phase of the reflex. It was hypothesized that an early onset of CLS pacing may be triggered&#xD;
        by the compensatory increase in heart rate to counteract vasodilation and pressure drop&#xD;
        during the pre-syncope phase of the reflex. The BIOSync study showed a 77% reduced risk of&#xD;
        syncope in the DDD-CLS group as compared to pacing off. The design of the BIOSync study did&#xD;
        not allow to assess the specific effect that CLS adds to dual-chamber pacing. Despite DDD-CLS&#xD;
        pacing, 22% of patients had syncopal recurrence in 2 years. Further investigations are&#xD;
        therefore needed in order to reduce this failure rate. Indeed, it is still unclear whether&#xD;
        syncopal recurrences should be ascribed to dominant vasodilation or if the CLS&#xD;
        programming/functioning needs optimization to more adequately sustain cardiac output during&#xD;
        reflex in these specific cases.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">September 29, 2022</start_date>
    <completion_date type="Actual">May 12, 2023</completion_date>
    <primary_completion_date type="Actual">May 12, 2023</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <target_duration>1 Day</target_duration>
    <primary_outcome>
      <measure>Heart rate [bpm] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Instantaneous measurement of heart rate value at specific time-points during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Systolic and diastolic blood pressure [mmHg] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Instantaneous measurement of blood pressure at specific time-points during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Stroke volume [ml] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Instantaneous measurement of stroke volume at specific time-points during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Peripheral resistance [dyn·s/cm5] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Instantaneous measurement of peripheral resistance at specific time-points during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time of maximum spontaneous heart rate [s]</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Recording of a specific time-point during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time of pacing onset [s]</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Recording of a specific time-point during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time of recovery of spontaneous rhythm after pacing [s]</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Recording of a specific time-point during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time of syncope [s]</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Recording of a specific time-point during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time of tilt-down [s]</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Recording of a specific time-point during HUTT examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Duration of the recovery phase [s]</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Interval from maximum pacing rate to basic rate or spontaneous rhythm</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Slope in heart rate [bpm per sec] during the recovery phase</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Calculation of the rate of change of heart rate from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Slope in systolic blood pressure (mmHg per sec) during the recovery phase</measure>
      <time_frame>From the start to the end of the HUTT examination, assessed up to 45 minutes</time_frame>
      <description>Calculation of the rate of change of systolic blood pressure from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery</description>
    </primary_outcome>
    <enrollment type="Actual">20</enrollment>
    <condition>Syncope</condition>
    <condition>Syncope, Vasovagal</condition>
    <eligibility>
      <study_pop>
        <textblock>
          Patients with reflex syncope and positive cardioinhibitory response to Head-Up Tilt Test&#xD;
          (HUTT) who had already participated in the BIOSync study.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion criteria&#xD;
  &#xD;
            -  Ability to understand the nature of the study.&#xD;
  &#xD;
            -  Willingness to provide written informed consent.&#xD;
  &#xD;
            -  Patients undergoing HUTT for monitoring of syncope, therapy adjustment, training or&#xD;
               other medical reasons during ordinary follow-up, irrespective of study participation&#xD;
  &#xD;
            -  Patients who participated in the BIOSync study*.&#xD;
  &#xD;
            -  Patients with a dual-chamber pacing system equipped with the CLS algorithm. * If&#xD;
               needed, inclusion of other patients who did not participate in the BIOSync study will&#xD;
               be considered to complete study cohort, provided that they have already a CLS&#xD;
               pacemaker system and fulfill the same inclusion/exclusion criteria of the BIOSync&#xD;
               study.&#xD;
  &#xD;
          Exclusion criteria&#xD;
  &#xD;
            -  Pregnant or breast feeding women.&#xD;
  &#xD;
            -  Age less than 40 years.&#xD;
  &#xD;
            -  Patients who after the BIOSync study participation have developed the following:&#xD;
  &#xD;
                 -  Any indication to pacemaker different from reflex syncope with positive HUTT&#xD;
                    response; or&#xD;
  &#xD;
                 -  Any classified indication to implantable defibrillator, cardiac resynchronization&#xD;
                    therapy according to current guidelines; or&#xD;
  &#xD;
                 -  Any cardiac dysfunctions likely leading to loss of consciousness (overt heart&#xD;
                    failure, ejection fraction &lt;40%, myocardial infarction, diagnosis of hypertrophic&#xD;
                    or dilated cardiomyopathy, clinically significant valvular disease, sinus&#xD;
                    bradycardia &lt;50 bpm or sinoatrial block, Mobitz I second degree atrioventricular&#xD;
                    block, Mobitz II second or third degree atrioventricular block, complete&#xD;
                    bundle-branch block).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Ospedale di Bolzano - Azienda Sanitaria dell'Alto Adige</name>
        <address>
          <city>Bolzano</city>
          <zip>39100</zip>
          <country>Italy</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Monaldi - AORN dei Colli - Università della Campania &quot;Luigi Vanvitelli&quot;</name>
        <address>
          <city>Napoli</city>
          <zip>80131</zip>
          <country>Italy</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>September 1, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Syncope</keyword>
    <keyword>Head-up Tilt Test</keyword>
    <keyword>Closed Loop Stimulation</keyword>
    <keyword>CLS</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Syncope</mesh_term>
      <mesh_term>Syncope, Vasovagal</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Data will be shared on request to the corresponding author with permission of BIOTRONIK SE &amp; Co. KG.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    </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/NCT06038708
  org study id: BA117
  nct id: NCT06038708
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to explore changes in patients' hemodynamic parameters during
        the Head-Up Tilt Test ("HUTT") and their timing with respect to onset of the Closed Loop
        Stimulation (CLS) pacing. This study aims to add knowledge to better understand the
        mechanisms underlying recurrent syncopal events and optimal pacing programming.
  The 2021 European Society of Cardiology guidelines recommend cardiac pacing in patients aged
        >40 years with tilt-induced asystolic reflex syncope (class I, level of evidence A). The
        recommendation relies on recent results from the multicentre, randomised, double-blinded,
        parallel-design BIOSync trial (NCT02324920). The BIOSync study provided evidence of benefit
        of dual chamber pacing in patients with tilt-induced reflex syncope and confirmed the role of
        Head-up Tilt Table (HUTT) test as a diagnostic method for cardiac pacing in reflex syncope.
        The Closed Loop Stimulation (CLS) is able to measure changes in intracardiac impedance during
        the systolic phase of each cardiac cycle which are strictly correlated to the increased heart
        rate and right ventricular contraction speed which are usually present during the pre-syncope
        phase of the reflex. It was hypothesized that an early onset of CLS pacing may be triggered
        by the compensatory increase in heart rate to counteract vasodilation and pressure drop
        during the pre-syncope phase of the reflex. The BIOSync study showed a 77% reduced risk of
        syncope in the DDD-CLS group as compared to pacing off. The design of the BIOSync study did
        not allow to assess the specific effect that CLS adds to dual-chamber pacing. Despite DDD-CLS
        pacing, 22% of patients had syncopal recurrence in 2 years. Further investigations are
        therefore needed in order to reduce this failure rate. Indeed, it is still unclear whether
        syncopal recurrences should be ascribed to dominant vasodilation or if the CLS
        programming/functioning needs optimization to more adequately sustain cardiac output during
        reflex in these specific cases.
  observational model: Cohort
  time perspective: Prospective
  measure: Heart rate [bpm] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Instantaneous measurement of heart rate value at specific time-points during HUTT examination
  measure: Systolic and diastolic blood pressure [mmHg] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Instantaneous measurement of blood pressure at specific time-points during HUTT examination
  measure: Stroke volume [ml] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Instantaneous measurement of stroke volume at specific time-points during HUTT examination
  measure: Peripheral resistance [dyn·s/cm5] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Instantaneous measurement of peripheral resistance at specific time-points during HUTT examination
  measure: Time of maximum spontaneous heart rate [s]
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Recording of a specific time-point during HUTT examination
  measure: Time of pacing onset [s]
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Recording of a specific time-point during HUTT examination
  measure: Time of recovery of spontaneous rhythm after pacing [s]
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Recording of a specific time-point during HUTT examination
  measure: Time of syncope [s]
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Recording of a specific time-point during HUTT examination
  measure: Time of tilt-down [s]
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Recording of a specific time-point during HUTT examination
  measure: Duration of the recovery phase [s]
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Interval from maximum pacing rate to basic rate or spontaneous rhythm
  measure: Slope in heart rate [bpm per sec] during the recovery phase
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Calculation of the rate of change of heart rate from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery
  measure: Slope in systolic blood pressure (mmHg per sec) during the recovery phase
  time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
  description: Calculation of the rate of change of systolic blood pressure from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  facility: 
  country: Italy
  responsible party type: Sponsor
  mesh term: Syncope
  mesh term: Syncope, Vasovagal
  sharing ipd: Yes
  ipd description: Data will be shared on request to the corresponding author with permission of BIOTRONIK SE & Co. KG.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)