<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/NCT04420065</url>
  </required_header>
  <id_info>
    <org_study_id>READAPT</org_study_id>
    <nct_id>NCT04420065</nct_id>
  </id_info>
  <brief_title>Effects of Preferential Left Ventricular Pacing on Ventriculoarterial Coupling and Clinical Course of Heart Failure</brief_title>
  <acronym>READAPT</acronym>
  <official_title>CompaRative Study of the Effects of Left ventriculAr and Biventricular Pacing on inDices of cArdiac Function and Clinical Course of Heart Failure PatienTs: Rationale and Design of the READAPT Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National and Kapodistrian University of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National and Kapodistrian University of Athens</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized trial of adult patients to study the effects of preferential left ventricular&#xD;
      pacing on ventriculoarterial coupling of both systemic and pulmonary circulation, indices of&#xD;
      systolic and diastolic function of both ventricles, and clinical course of patients with&#xD;
      advances dyssynchronous heart failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study hypothesis is that preferential left ventricular (LV) pacing, delivered by means of the&#xD;
      AdaptivCRT® algorithm and in conjunction with automated V-V delay adjustments, will lead to&#xD;
      improvements over standard biventricular pacing (BVP) in the function of all cardiac&#xD;
      chambers, reduce arrhythmic burden, improve ventricular-arterial coupling (VAC), and patient&#xD;
      functional status. It would be interesting to study what changes in right-side VAC (RVAC) can&#xD;
      be appreciated with the activation of the preferential LV pacing algorithm and how they&#xD;
      relate to each other, i.e. whether LV is driven towards maximizing output whilst RV shifts to&#xD;
      optimizing energy efficiency.&#xD;
&#xD;
      READAPT is a single-center, prospective, randomized trial of heart failure patients eligible&#xD;
      for CRT according to current European heart failure guidelines. Informed written consent is&#xD;
      required from all study participants.&#xD;
&#xD;
      Adult (aged 18-80 years old), consenting patients with any cardiomyopathy type, diagnosed at&#xD;
      least 6 months prior (to exclude recent myocarditis cases that may remit and confound&#xD;
      outcomes), on optimal medical therapy for at least 3 months, and an existing I/IIa indication&#xD;
      for a cardiac resynchronization therapy - defibrillator (CRT-D) device will be enrolled and&#xD;
      randomized into 2 groups, one receiving standard CRT (Group 1 - G1), and one with activation&#xD;
      of the preferential LV pacing algorithm (Group 2 - G2). Enrollment date will amount to the&#xD;
      baseline assessment date, with device implantation occurring preferably within 48 hours.&#xD;
      READAPT will include patients with both new CRT-D implantation and an upgrade from an&#xD;
      existing defibrillator or pacemaker with no prior left ventricular lead placement.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">September 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients randomized after enrollment to receive either standard biventricular pacing, or preferential left ventricular pacing (left ventricle will be resynchronized, but right ventricle will be activated through the intrinsic conduction system)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Patient and assessor unaware of chosen programming mode and activated algorithms. The standard of care that is biventricular pacing will be provided to all participants.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in patient exercise capacity</measure>
    <time_frame>12 months</time_frame>
    <description>Assessed by cardiopulmonary exercise test in terms of maximal oxygen consumption in ml/kg/min</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of hospitalizations for heart failure</measure>
    <time_frame>12 months</time_frame>
    <description>Data retrieved from online patient file will be used to compare number of unplanned hospitalizations for worsening heart failure between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular function</measure>
    <time_frame>12 months</time_frame>
    <description>Assessed by ejection fraction (in %), strain echocardiography - changes in % global longitudinal peak strain and diastolic function indices (E/e')</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Right ventricular function</measure>
    <time_frame>12 months</time_frame>
    <description>Assessed by strain echocardiography in terms of two-dimensional % global longitudinal peak strain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventriculoarterial coupling for both systemic and pulmonary circulation</measure>
    <time_frame>12 months</time_frame>
    <description>Assessed by the noninvasive single-beat echocardiographic method in terms of distance from 1 (value associated with maximization of stroke work for a given contractility)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">220</enrollment>
  <condition>Heart Failure With Reduced Ejection Fraction</condition>
  <arm_group>
    <arm_group_label>Classical biventricular pacing</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Commercially available LV-pacing capable CRT devices and quadripolar leads will be implanted. Right ventricular (RV) and right atrial (RA) leads will be placed according to standard practice. The LV lead will also be placed according to standard practice, targeting to a lateral, posterolateral, or anterolateral branch of the coronary sinus (CS). Interventricular delay programmed will be determined based on stroke volume maximization, and will be used as a criterion for BVP optimization. Atrioventricular delay optimization shall be automatically performed by the device.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Preferential left ventricular pacing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In G2 patients, an algorithm for preferential left ventricular pacing will be activated. Following selection of the dipole maximizing stroke volume during simultaneous LV-RV pacing, subsequent V-V delay optimization shall be delegated to the algorithm. Based on previous studies, a subgroup analysis of G2 will be performed, comparing those receiving ≥50% with those receiving &lt;50% preferential LV pacing evaluated over the total duration of the study (12 months).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Preferential left ventricular pacing</intervention_name>
    <description>Activation of an algorithm attempting to provide preferential left ventricular pacing in an anticipatory manner, thus potentially preventing iatrogenic, pacing-related, right ventricular dysfunction, and improving coupling and outcomes in dyssynchronous heart failure patients</description>
    <arm_group_label>Preferential left ventricular pacing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Biventricular pacing</intervention_name>
    <description>Standard biventricular pacing, with V-V delay programmed based on stroke volume maximization, and A-V delay delegated to the device</description>
    <arm_group_label>Classical biventricular pacing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Age 18-80 years old Provided informed consent Any cardiomyopathy type, diagnosed at least 6&#xD;
        months prior (to exclude recent myocarditis cases that may remit and confound outcomes) On&#xD;
        optimal medical therapy for at least 3 months, An existing I/IIa indication for a CRT-D&#xD;
        device Both new CRT-D implantation and an upgrade from an existing ICD or pacemaker with no&#xD;
        prior left ventricular lead placement.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have an existing Class I recalled lead,&#xD;
&#xD;
          2. Are anticipated to need heart transplantation within the next 9 months,&#xD;
&#xD;
          3. Have undergone cardiac transplantation less than 40 days prior to enrolment,&#xD;
&#xD;
          4. Have had a cerebrovascular accident or transient ischemic attack within 3 months of&#xD;
             enrollment,&#xD;
&#xD;
          5. Have had a recent myocardial infarction less than 40 days prior to enrollment, or&#xD;
             unstable angina or cardiac revascularization less than 3 months prior to enrolment,&#xD;
&#xD;
          6. Have documented moderate to severe/severe mitral/aortic/tricuspid/pulmonary&#xD;
             insufficiency (noninvasive VAC calculation impossible),&#xD;
&#xD;
          7. Exhibit a daily burden of premature ventricular complexes (PVCs) of either ≥10% of&#xD;
             total QRSs or ≥10,000 on ambulatory ECG recording21, 22 (to exclude PVC-related,&#xD;
             potentially reversible cardiomyopathy),&#xD;
&#xD;
          8. Are currently participating in a clinical investigation that includes an active&#xD;
             treatment arm,&#xD;
&#xD;
          9. Have diagnosed pulmonary hypertension other than class II (left heart-related),&#xD;
&#xD;
         10. Have known stage IV-V renal dysfunction (clearance estimated by the Cockcroft-Gault&#xD;
             equation),&#xD;
&#xD;
         11. Have permanent atrial fibrillation,&#xD;
&#xD;
         12. Have complete atrioventricular block,&#xD;
&#xD;
         13. Have a prolonged (&gt;200msec) PQ interval on surface ECG (thus invalidating the option&#xD;
             for preferential LV pacing),&#xD;
&#xD;
         14. Are pregnant or planning to become pregnant during the duration of the study (in case&#xD;
             of unplanned pregnancy the patient will have to be excluded from the study),&#xD;
&#xD;
         15. Have an expected life expectancy of &lt;12 months, or&#xD;
&#xD;
         16. Undergo major adaptations to their pharmacological regimens during follow-up (e.g.&#xD;
             initiation of neprilysin inhibitors).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Christina Chrysohoou, MD PhD</last_name>
    <phone>00306944435168</phone>
    <email>chrysohoou@usa.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Christos-Konstantinos Antoniou, MD PhD</last_name>
    <phone>00306972708430</phone>
    <email>ckantoniou@hotmail.gr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>First University Department of Cardiology, Hippokrateion General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <contact>
      <last_name>Manina Anastasopoulou</last_name>
      <phone>00302132088027</phone>
    </contact>
    <investigator>
      <last_name>Polychronis Dilaveris, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christina Chrysohoou, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christos-Konstantinos Antoniou, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Konstantinos Konstantinou, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Panagiotis Xydis, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Panagiota Manolakou, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Dimitrios Tousoulis, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 3, 2020</last_update_submitted>
  <last_update_submitted_qc>June 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National and Kapodistrian University of Athens</investigator_affiliation>
    <investigator_full_name>Christina Chrysohoou</investigator_full_name>
    <investigator_title>Cardiology Consultant, Director of Cardiology, Senior Researcher</investigator_title>
  </responsible_party>
  <keyword>Heart failure</keyword>
  <keyword>Cardiac resynchronization therapy</keyword>
  <keyword>Preferential left ventricular pacing</keyword>
  <keyword>Ventriculoarterial coupling</keyword>
  <keyword>Echocardiography</keyword>
  <keyword>Cardiopulmonary exercise test</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Disease Progression</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Study design data and anonymized individual data allowing for pooling in subsequent analyses</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data to be shared 2 years after study completion</ipd_time_frame>
    <ipd_access_criteria>Request made by investigator with an active, registered clinical trial</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04420065
org study id: READAPT
nct id: NCT04420065
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Randomized trial of adult patients to study the effects of preferential left ventricular
      pacing on ventriculoarterial coupling of both systemic and pulmonary circulation, indices of
      systolic and diastolic function of both ventricles, and clinical course of patients with
      advances dyssynchronous heart failure.
Study hypothesis is that preferential left ventricular (LV) pacing, delivered by means of the
      AdaptivCRT® algorithm and in conjunction with automated V-V delay adjustments, will lead to
      improvements over standard biventricular pacing (BVP) in the function of all cardiac
      chambers, reduce arrhythmic burden, improve ventricular-arterial coupling (VAC), and patient
      functional status. It would be interesting to study what changes in right-side VAC (RVAC) can
      be appreciated with the activation of the preferential LV pacing algorithm and how they
      relate to each other, i.e. whether LV is driven towards maximizing output whilst RV shifts to
      optimizing energy efficiency.

      READAPT is a single-center, prospective, randomized trial of heart failure patients eligible
      for CRT according to current European heart failure guidelines. Informed written consent is
      required from all study participants.

      Adult (aged 18-80 years old), consenting patients with any cardiomyopathy type, diagnosed at
      least 6 months prior (to exclude recent myocarditis cases that may remit and confound
      outcomes), on optimal medical therapy for at least 3 months, and an existing I/IIa indication
      for a cardiac resynchronization therapy - defibrillator (CRT-D) device will be enrolled and
      randomized into 2 groups, one receiving standard CRT (Group 1 - G1), and one with activation
      of the preferential LV pacing algorithm (Group 2 - G2). Enrollment date will amount to the
      baseline assessment date, with device implantation occurring preferably within 48 hours.
      READAPT will include patients with both new CRT-D implantation and an upgrade from an
      existing defibrillator or pacemaker with no prior left ventricular lead placement.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients randomized after enrollment to receive either standard biventricular pacing, or preferential left ventricular pacing (left ventricle will be resynchronized, but right ventricle will be activated through the intrinsic conduction system)
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: Patient and assessor unaware of chosen programming mode and activated algorithms. The standard of care that is biventricular pacing will be provided to all participants.
measure: Changes in patient exercise capacity
time frame: 12 months
description: Assessed by cardiopulmonary exercise test in terms of maximal oxygen consumption in ml/kg/min
measure: Number of hospitalizations for heart failure
time frame: 12 months
description: Data retrieved from online patient file will be used to compare number of unplanned hospitalizations for worsening heart failure between groups
measure: Left ventricular function
time frame: 12 months
description: Assessed by ejection fraction (in %), strain echocardiography - changes in % global longitudinal peak strain and diastolic function indices (E/e')
measure: Right ventricular function
time frame: 12 months
description: Assessed by strain echocardiography in terms of two-dimensional % global longitudinal peak strain
measure: Ventriculoarterial coupling for both systemic and pulmonary circulation
time frame: 12 months
description: Assessed by the noninvasive single-beat echocardiographic method in terms of distance from 1 (value associated with maximization of stroke work for a given contractility)
arm group label: Classical biventricular pacing
arm group type: Active Comparator
description: Commercially available LV-pacing capable CRT devices and quadripolar leads will be implanted. Right ventricular (RV) and right atrial (RA) leads will be placed according to standard practice. The LV lead will also be placed according to standard practice, targeting to a lateral, posterolateral, or anterolateral branch of the coronary sinus (CS). Interventricular delay programmed will be determined based on stroke volume maximization, and will be used as a criterion for BVP optimization. Atrioventricular delay optimization shall be automatically performed by the device.
arm group label: Preferential left ventricular pacing
arm group type: Experimental
description: In G2 patients, an algorithm for preferential left ventricular pacing will be activated. Following selection of the dipole maximizing stroke volume during simultaneous LV-RV pacing, subsequent V-V delay optimization shall be delegated to the algorithm. Based on previous studies, a subgroup analysis of G2 will be performed, comparing those receiving ≥50% with those receiving <50% preferential LV pacing evaluated over the total duration of the study (12 months).
intervention type: Device
intervention name: Preferential left ventricular pacing
description: Activation of an algorithm attempting to provide preferential left ventricular pacing in an anticipatory manner, thus potentially preventing iatrogenic, pacing-related, right ventricular dysfunction, and improving coupling and outcomes in dyssynchronous heart failure patients
arm group label: Preferential left ventricular pacing
intervention type: Device
intervention name: Biventricular pacing
description: Standard biventricular pacing, with V-V delay programmed based on stroke volume maximization, and A-V delay delegated to the device
arm group label: Classical biventricular pacing
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Christina Chrysohoou, MD PhD
phone: 00306944435168
email: chrysohoou@usa.net
last name: Christos-Konstantinos Antoniou, MD PhD
phone: 00306972708430
email: ckantoniou@hotmail.gr
facility: 
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Greece
responsible party type: Principal Investigator
investigator affiliation: National and Kapodistrian University of Athens
investigator full name: Christina Chrysohoou
investigator title: Cardiology Consultant, Director of Cardiology, Senior Researcher
mesh term: Heart Failure
mesh term: Disease Progression
sharing ipd: Yes
ipd description: Study design data and anonymized individual data allowing for pooling in subsequent analyses
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data to be shared 2 years after study completion
ipd access criteria: Request made by investigator with an active, registered clinical trial