<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/NCT03757377</url>
  </required_header>
  <id_info>
    <org_study_id>CS-03 Ver 3.0</org_study_id>
    <nct_id>NCT03757377</nct_id>
  </id_info>
  <brief_title>Moderato System in Patients With Hypertension</brief_title>
  <official_title>Clinical Evaluation of Safety and Effectiveness of the BackBeat Medical Moderato System in Patients With Hypertension: A Double-Blind Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BackBeat Medical Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>MLM Medical Labs GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>nabios GmbH</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>BackBeat Medical Inc</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 purpose of this double blind randomized study is the evaluation of the safety and&#xD;
      efficacy of the Moderato System. The Moderato implantable pulse generator is indicated for&#xD;
      patients who have hypertension and also require a dual chamber pacemaker in order to reduce&#xD;
      their blood pressure.&#xD;
&#xD;
      In this amended CS-03 protocol Version 3.0, the study will evaluate the safety and efficacy&#xD;
      in a randomized, double-blind study following active treatment vs. a control patient&#xD;
      population for a period of 3 month for efficacy and 12 months for safety (In comparison to 6&#xD;
      months for patients under protocol CS-03 Ver 1.1, NCT02837445).&#xD;
&#xD;
      The device will be considered to have a clinical effectiveness with regard to its&#xD;
      anti-hypertension function if there is a statistically significant and clinically meaningful&#xD;
      reduction in mean 24-hour ambulatory systolic blood pressure in the treatment group compared&#xD;
      to the control group. The primary efficacy endpoint will be evaluated 3 months after&#xD;
      randomization. The Primary safety analysis will compare the treatment and the control after&#xD;
      12 months of treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Protocol CS-03 Ver 1.1 (NCT02837445) was amended at the advice of the Scientific Advisory to&#xD;
      protocol CS-03 Version 3.0 with more stringent hypertension inclusion criteria and different&#xD;
      observation intervals for efficacy and safety.&#xD;
&#xD;
      In CS-03 Version 3.0 the time of the primary efficacy endpoint was reduced from 6 months to 3&#xD;
      months post randomization which was deemed a suitable interval for the chronic effect,&#xD;
      whereas for the safety endpoint, the period was lengthened to 12 months post randomization to&#xD;
      better monitor potential risks of the treatment on cardiac function (Blinding period was&#xD;
      increased from 6 months to 12 months). Protocols were thus split in order to allow better&#xD;
      clarification to the difference in the time to the primary endpoints for efficacy and safety&#xD;
      between the two CIP versions and simplify data analysis.&#xD;
&#xD;
      Protocol Ver 3.0 prescribes data analysis of all patients randomized under version 1.1 to be&#xD;
      performed once they complete the 6 months follow-up as set in protocol version 1.1&#xD;
      (NCT0283744). It is expected that ~40 patients will be randomized according to protocol&#xD;
      version 1.1 prior to the enrollment of patients according to protocol version 3.0. The&#xD;
      results will be considered as interim analysis.&#xD;
&#xD;
      The recruitment for the protocol version 1.1 is now completed. Total of 47 patients were&#xD;
      randomized according to protocol version 1.1 and all patients completed the follow-up period&#xD;
      for the primary endpoint.&#xD;
&#xD;
      Patients are currently being followed up for the study &quot;extension period&quot;.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 30, 2017</start_date>
  <completion_date type="Anticipated">March 30, 2023</completion_date>
  <primary_completion_date type="Actual">February 1, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double (Participant, Investigator)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of composite of major cardiac events</measure>
    <time_frame>12 months post Randomization</time_frame>
    <description>including heart failure, clinically significant arrhythmias eg, persistent or increased atrial fibrillation, serious ventricular arrhythmias, myocardial infarction, stroke, heart failure, renal failure and/or related safety events that result in death</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in average 24 hour systolic ambulatory blood pressure</measure>
    <time_frame>Week 3 pre Randomization and 3 months post Randomization</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">203</enrollment>
  <condition>Hypertension, Resistant to Conventional Therapy</condition>
  <condition>Atrioventricular Block</condition>
  <arm_group>
    <arm_group_label>BackBeat Moderato System (PHC ON)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Eligible patients randomized after optimization phase to PHC ON (PHC algorithm active) for 12 months. Patients continue standard or modified anti-hypertension medical regime at discretion of the investigator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BackBeat Moderato System (PHC OFF)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Eligible patients randomized after optimization phase to pacemaker only (PHC OFF or PHC algorithm not active) for 12 months. Patients continue standard or modified anti-hypertension medical regime at discretion of the investigator.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>BackBeat Moderato System</intervention_name>
    <description>Eligible patients randomized after optimization phase to PHC ON for 12 months. Patients continue standard or modified anti-hypertension medical regime at discretion of the investigator</description>
    <arm_group_label>BackBeat Moderato System (PHC ON)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>BackBeat Moderato Sytsem</intervention_name>
    <description>Eligible patients randomized after optimization phase to PHC OFF for 12 months. Patients continue standard or modified anti-hypertension medical regime at discretion of the investigator.</description>
    <arm_group_label>BackBeat Moderato System (PHC OFF)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Requirement of dual chamber pacemaker or upgrade from a single chamber to a dual&#xD;
             chamber pacemaker.&#xD;
&#xD;
          -  Stable (at least 6 weeks) hypertension treatment with at least 1 anti-hypertensive&#xD;
             drug, which is anticipated to be maintained without changes. Stable is defined as&#xD;
             being in the same drug regimen, and the dose of each drug(s) no more than 50% reduced&#xD;
             or 100% increased over the past 6 weeks.&#xD;
&#xD;
          -  Average 24-hour ambulatory systolic blood pressure ≥ 130 mmHg (with directly observed&#xD;
             medical therapy, DOT) and office blood pressure ≥140 mmHg.&#xD;
&#xD;
          -  Subject is able to comply with study visits for at least 13 months (e.g., is capable&#xD;
             and willing to travel to/from the center for all scheduled study visits).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known secondary cause of HTN.&#xD;
&#xD;
          -  Average ambulatory or office systolic BP &gt; 195 mmHg.&#xD;
&#xD;
          -  Permanent atrial fibrillation.&#xD;
&#xD;
          -  History of significant paroxysmal atrial fibrillation/flutter burden (defined as &gt;25%&#xD;
             of beats).&#xD;
&#xD;
          -  Cardiac ejection fraction &lt;50%.&#xD;
&#xD;
          -  Symptoms of heart failure, NYHA Class II or greater.&#xD;
&#xD;
          -  Hypertrophic cardiomyopathy, restrictive cardiomyopathy or inter-ventricular septal&#xD;
             thickness ≥ 15 mm.&#xD;
&#xD;
          -  Subject is on dialysis.&#xD;
&#xD;
          -  Subject has an estimated Glomerular Filtration Rate &lt; 30 ml/min/1.73 m²&#xD;
&#xD;
          -  Prior neurological events (stroke or TIA) within the past year or events at a prior&#xD;
             time that has resulted in residual neurologic deficit.&#xD;
&#xD;
          -  Carotid artery disease.&#xD;
&#xD;
          -  Known autonomic dysfunction.&#xD;
&#xD;
          -  History of clinically significant untreated ventricular tachyarrhythmia or has&#xD;
             experienced cardiac arrest.&#xD;
&#xD;
          -  Previous active device-based treatment for HTN.&#xD;
&#xD;
          -  Existing implant, other than a pacemaker that needs replacing.&#xD;
&#xD;
          -  Subject is or has the possibility of becoming pregnant and is unwilling of&#xD;
             contraception during the study.&#xD;
&#xD;
          -  Subject is unwilling or cannot provide Informed Consent&#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_official>
    <last_name>Karl-Heinz Kuck, Prof. MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asklepios Klinik St. Georg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UZ Brussel - Heart Rhythm Management Center</name>
      <address>
        <city>Brussels</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vilnius University Hospital Santariskiu Klinikos</name>
      <address>
        <city>Vilnius</city>
        <zip>08661</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielnym Publicznym Centralnym Szpitalem Klinicznym</name>
      <address>
        <city>Warsaw</city>
        <zip>02-097</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Silesian Center for Heart Diseases</name>
      <address>
        <city>Zabrze</city>
        <zip>41-800</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Lithuania</country>
    <country>Poland</country>
  </location_countries>
  <removed_countries>
    <country>United Kingdom</country>
  </removed_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/?term=29628351</url>
    <description>Rationale and evidence for the development of a durable device-based cardiac neuromodulation therapy for hypertension.</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/?term=29275370</url>
    <description>Pacemaker-Mediated Programmable Hypertension Control Therapy.</description>
  </link>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>December 12, 2022</last_update_submitted>
  <last_update_submitted_qc>December 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Atrioventricular Block</mesh_term>
  </condition_browse>
  <!-- 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/NCT03757377
org study id: CS-03 Ver 3.0
nct id: NCT03757377
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this double blind randomized study is the evaluation of the safety and
      efficacy of the Moderato System. The Moderato implantable pulse generator is indicated for
      patients who have hypertension and also require a dual chamber pacemaker in order to reduce
      their blood pressure.

      In this amended CS-03 protocol Version 3.0, the study will evaluate the safety and efficacy
      in a randomized, double-blind study following active treatment vs. a control patient
      population for a period of 3 month for efficacy and 12 months for safety (In comparison to 6
      months for patients under protocol CS-03 Ver 1.1, NCT02837445).

      The device will be considered to have a clinical effectiveness with regard to its
      anti-hypertension function if there is a statistically significant and clinically meaningful
      reduction in mean 24-hour ambulatory systolic blood pressure in the treatment group compared
      to the control group. The primary efficacy endpoint will be evaluated 3 months after
      randomization. The Primary safety analysis will compare the treatment and the control after
      12 months of treatment.
Protocol CS-03 Ver 1.1 (NCT02837445) was amended at the advice of the Scientific Advisory to
      protocol CS-03 Version 3.0 with more stringent hypertension inclusion criteria and different
      observation intervals for efficacy and safety.

      In CS-03 Version 3.0 the time of the primary efficacy endpoint was reduced from 6 months to 3
      months post randomization which was deemed a suitable interval for the chronic effect,
      whereas for the safety endpoint, the period was lengthened to 12 months post randomization to
      better monitor potential risks of the treatment on cardiac function (Blinding period was
      increased from 6 months to 12 months). Protocols were thus split in order to allow better
      clarification to the difference in the time to the primary endpoints for efficacy and safety
      between the two CIP versions and simplify data analysis.

      Protocol Ver 3.0 prescribes data analysis of all patients randomized under version 1.1 to be
      performed once they complete the 6 months follow-up as set in protocol version 1.1
      (NCT0283744). It is expected that ~40 patients will be randomized according to protocol
      version 1.1 prior to the enrollment of patients according to protocol version 3.0. The
      results will be considered as interim analysis.

      The recruitment for the protocol version 1.1 is now completed. Total of 47 patients were
      randomized according to protocol version 1.1 and all patients completed the follow-up period
      for the primary endpoint.

      Patients are currently being followed up for the study "extension period".
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double (Participant, Investigator)
measure: Rate of composite of major cardiac events
time frame: 12 months post Randomization
description: including heart failure, clinically significant arrhythmias eg, persistent or increased atrial fibrillation, serious ventricular arrhythmias, myocardial infarction, stroke, heart failure, renal failure and/or related safety events that result in death
measure: Change in average 24 hour systolic ambulatory blood pressure
time frame: Week 3 pre Randomization and 3 months post Randomization
arm group label: BackBeat Moderato System (PHC ON)
arm group type: Active Comparator
description: Eligible patients randomized after optimization phase to PHC ON (PHC algorithm active) for 12 months. Patients continue standard or modified anti-hypertension medical regime at discretion of the investigator.
arm group label: BackBeat Moderato System (PHC OFF)
arm group type: Placebo Comparator
description: Eligible patients randomized after optimization phase to pacemaker only (PHC OFF or PHC algorithm not active) for 12 months. Patients continue standard or modified anti-hypertension medical regime at discretion of the investigator.
intervention type: Device
intervention name: BackBeat Moderato System
description: Eligible patients randomized after optimization phase to PHC ON for 12 months. Patients continue standard or modified anti-hypertension medical regime at discretion of the investigator
arm group label: BackBeat Moderato System (PHC ON)
intervention type: Device
intervention name: BackBeat Moderato Sytsem
description: Eligible patients randomized after optimization phase to PHC OFF for 12 months. Patients continue standard or modified anti-hypertension medical regime at discretion of the investigator.
arm group label: BackBeat Moderato System (PHC OFF)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Karl-Heinz Kuck, Prof. MD
role: Principal Investigator
affiliation: Asklepios Klinik St. Georg
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Lithuania
country: Poland
country: United Kingdom
url: https://www.ncbi.nlm.nih.gov/pubmed/?term=29628351
description: Rationale and evidence for the development of a durable device-based cardiac neuromodulation therapy for hypertension.
url: https://www.ncbi.nlm.nih.gov/pubmed/?term=29275370
description: Pacemaker-Mediated Programmable Hypertension Control Therapy.
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Atrioventricular Block