<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/NCT03230643</url>
  </required_header>
  <id_info>
    <org_study_id>HDZ-KA_012_DG</org_study_id>
    <nct_id>NCT03230643</nct_id>
  </id_info>
  <brief_title>Evaluation of Baroreflex Activation Therapy in Patients With Advanced Heart Failure</brief_title>
  <official_title>Evaluation of Baroreflex Activation Therapy in Patients With Advanced Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heart and Diabetes Center North-Rhine Westfalia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Heart and Diabetes Center North-Rhine Westfalia</source>
  <oversight_info>
    <has_dmc>No</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 objective of this single center prospective clinical trial is to evaluate the safety and&#xD;
      efficacy of carotid Baroreflex Activation Therapy (BAT) in advanced heart failure (HFrEF).&#xD;
      Beyond that, the primary aim of this study is to identify patients of the whole HFrEF&#xD;
      population that are most likely to benefit from this new promising therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Baroreflex activation therapy (BAT) is a new treatment option for patients (pts) suffering&#xD;
      from heart failure with reduced left ventricular ejection fraction (HFrEF) to improve&#xD;
      functional status and quality of life. Yet it is unknown which pts of the whole HFrEF&#xD;
      population are most likely to benefit from this new promising therapy. As this invasive&#xD;
      technique should definitely not be proposed for all HFrEF pts with left ventricular ejection&#xD;
      fraction of 35 % or less the aim of this single center prospective clinical trial is to&#xD;
      evaluate to which extent possible factors (e.g. cardiac resynchronization therapy (CRT),&#xD;
      atrial fibrillation) may influence the response to BAT. To analyze any possible differences&#xD;
      concerning the modulation of the autonomic nervous system caused by BAT in the presence of&#xD;
      atrial fibrillation or cardiac resynchronization therapy, heart rate variability (HRV)&#xD;
      analyses will be performed additionally. As autonomic nervous activity plays a pivotal role&#xD;
      in the genesis and termination of atrial fibrillation any possible impact of baroreflex&#xD;
      activation therapy on atrial fibrillation will be examined.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">May 31, 2020</completion_date>
  <primary_completion_date type="Actual">October 15, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in left ventricular ejection fraction</measure>
    <time_frame>measured baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Quality of life</measure>
    <time_frame>assessed baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in NYHA functional class ranking</measure>
    <time_frame>measured baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Chance in exercise capacity (distance walked in 6 min)</measure>
    <time_frame>measured baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in N-terminal pro-brain natriuretic peptide</measure>
    <time_frame>measured baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation</time_frame>
  </primary_outcome>
  <enrollment type="Actual">40</enrollment>
  <condition>Heart Failure</condition>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Barostim neo implantation</intervention_name>
    <description>The Barostim neo Implantation is a new promising treatment option for patients with advanced heart failure (HEFrEF) as it might improve cardiac and vascular function by restoring sympathovagal-balance through its effects on the autonomic nervous system.&#xD;
In this observational study, data from patients who have received the Barostim neo System as part of clinical routine will be collected and analyzed. The implantation of this new device is not part of the study.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All patients suffering from advanced heart failure with left ventricular ejection fraction&#xD;
        of 35 % or less are eligible for this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  chronic heart failure (NYHA functional class III)&#xD;
&#xD;
          -  LVEF of 35% or less&#xD;
&#xD;
          -  chronic stable Guideline-directed medical therapy (diuretic agent,&#xD;
             angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and a beta&#xD;
             blocker, if tolerated)&#xD;
&#xD;
          -  resting heart rate between 60 and 100 beats/min&#xD;
&#xD;
          -  systolic blood pressure of at least 100 mmHg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  estimated glomerular filtration rate &lt; 30 ml/min/1.73 m²&#xD;
&#xD;
          -  Plaque and atherosclerosis reducing the linear diameter of the internal or distal&#xD;
             common carotid arteries by 50% or more&#xD;
&#xD;
          -  acute pulmonary edema within the last six weeks&#xD;
&#xD;
          -  implantation of Pacemakers, ICDs or CRTs within the last 3 months or planned for the&#xD;
             next three months&#xD;
&#xD;
          -  life expectancy &lt; 1 year&#xD;
&#xD;
          -  body mass index &gt; 40 kg/m²&#xD;
&#xD;
          -  symptomatic uncontrolled bradyarrhythmias&#xD;
&#xD;
          -  severe asthma, chronic obstructive pulmonary disease or restrictive lung disease&#xD;
&#xD;
          -  active malignancy&#xD;
&#xD;
          -  pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Herz- und Diabeteszentrum NRW</name>
      <address>
        <city>Bad Oeynhausen</city>
        <zip>32545</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <results_reference>
    <citation>DeMazumder D, Kass DA, O'Rourke B, Tomaselli GF. Cardiac resynchronization therapy restores sympathovagal balance in the failing heart by differential remodeling of cholinergic signaling. Circ Res. 2015 May 8;116(10):1691-9. doi: 10.1161/CIRCRESAHA.116.305268. Epub 2015 Mar 2.</citation>
    <PMID>25733594</PMID>
  </results_reference>
  <results_reference>
    <citation>Gronda E, Seravalle G, Trevano FQ, Costantino G, Casini A, Alsheraei A, Lovett EG, Vanoli E, Mancia G, Grassi G. Long-term chronic baroreflex activation: persistent efficacy in patients with heart failure and reduced ejection fraction. J Hypertens. 2015 Aug;33(8):1704-8. doi: 10.1097/HJH.0000000000000603.</citation>
    <PMID>26132760</PMID>
  </results_reference>
  <results_reference>
    <citation>Abraham WT, Zile MR, Weaver FA, Butter C, Ducharme A, Halbach M, Klug D, Lovett EG, Muller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Little WC. Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction. JACC Heart Fail. 2015 Jun;3(6):487-496. doi: 10.1016/j.jchf.2015.02.006. Epub 2015 May 14.</citation>
    <PMID>25982108</PMID>
  </results_reference>
  <results_reference>
    <citation>Zile MR, Abraham WT, Weaver FA, Butter C, Ducharme A, Halbach M, Klug D, Lovett EG, Muller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Little WC. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy. Eur J Heart Fail. 2015 Oct;17(10):1066-74. doi: 10.1002/ejhf.299. Epub 2015 Jun 10.</citation>
    <PMID>26011593</PMID>
  </results_reference>
  <results_reference>
    <citation>Fantoni C, Raffa S, Regoli F, Giraldi F, La Rovere MT, Prentice J, Pastori F, Fratini S, Salerno-Uriarte JA, Klein HU, Auricchio A. Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure. J Am Coll Cardiol. 2005 Nov 15;46(10):1875-82. doi: 10.1016/j.jacc.2005.06.081. Epub 2005 Oct 24.</citation>
    <PMID>16286175</PMID>
  </results_reference>
  <results_reference>
    <citation>Oliveira M. Comment on &quot;Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction&quot;. Rev Port Cardiol. 2015 Dec;34(12):795-7. doi: 10.1016/j.repce.2015.12.014.</citation>
    <PMID>27099884</PMID>
  </results_reference>
  <results_reference>
    <citation>Huang JH, Lin YK, Hsieh MH, Chen SA, Chiu WC, Chen YJ. Modulation of Autonomic Nervous Activity in the Termination of Paroxysmal Atrial Fibrillation. Pacing Clin Electrophysiol. 2017 Apr;40(4):401-408. doi: 10.1111/pace.13045. Epub 2017 Mar 3.</citation>
    <PMID>28181276</PMID>
  </results_reference>
  <results_reference>
    <citation>Linz D, Hohl M, Khoshkish S, Mahfoud F, Ukena C, Neuberger HR, Wirth K, Bohm M. Low-Level But Not High-Level Baroreceptor Stimulation Inhibits Atrial Fibrillation in a Pig Model of Sleep Apnea. J Cardiovasc Electrophysiol. 2016 Sep;27(9):1086-92. doi: 10.1111/jce.13020. Epub 2016 Jun 22.</citation>
    <PMID>27235276</PMID>
  </results_reference>
  <results_reference>
    <citation>Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger HR, Wirth K, Bohm M. Effects of electrical stimulation of carotid baroreflex and renal denervation on atrial electrophysiology. J Cardiovasc Electrophysiol. 2013 Sep;24(9):1028-33. doi: 10.1111/jce.12171. Epub 2013 May 2.</citation>
    <PMID>23638844</PMID>
  </results_reference>
  <results_reference>
    <citation>Dai M, Bao M, Zhang Y, Yu L, Cao Q, Tang Y, Huang H, Wang X, Hu D, Huang C. Low-level carotid baroreflex stimulation suppresses atrial fibrillation by inhibiting left stellate ganglion activity in an acute canine model. Heart Rhythm. 2016 Nov;13(11):2203-2212. doi: 10.1016/j.hrthm.2016.08.021. Epub 2016 Aug 9.</citation>
    <PMID>27520541</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>August 6, 2020</last_update_submitted>
  <last_update_submitted_qc>August 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2020</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>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03230643
org study id: HDZ-KA_012_DG
nct id: NCT03230643
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of this single center prospective clinical trial is to evaluate the safety and
      efficacy of carotid Baroreflex Activation Therapy (BAT) in advanced heart failure (HFrEF).
      Beyond that, the primary aim of this study is to identify patients of the whole HFrEF
      population that are most likely to benefit from this new promising therapy.
Baroreflex activation therapy (BAT) is a new treatment option for patients (pts) suffering
      from heart failure with reduced left ventricular ejection fraction (HFrEF) to improve
      functional status and quality of life. Yet it is unknown which pts of the whole HFrEF
      population are most likely to benefit from this new promising therapy. As this invasive
      technique should definitely not be proposed for all HFrEF pts with left ventricular ejection
      fraction of 35 % or less the aim of this single center prospective clinical trial is to
      evaluate to which extent possible factors (e.g. cardiac resynchronization therapy (CRT),
      atrial fibrillation) may influence the response to BAT. To analyze any possible differences
      concerning the modulation of the autonomic nervous system caused by BAT in the presence of
      atrial fibrillation or cardiac resynchronization therapy, heart rate variability (HRV)
      analyses will be performed additionally. As autonomic nervous activity plays a pivotal role
      in the genesis and termination of atrial fibrillation any possible impact of baroreflex
      activation therapy on atrial fibrillation will be examined.
observational model: Case-Control
time perspective: Prospective
measure: Change in left ventricular ejection fraction
time frame: measured baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation
measure: Change in Quality of life
time frame: assessed baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation
measure: Change in NYHA functional class ranking
time frame: measured baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation
measure: Chance in exercise capacity (distance walked in 6 min)
time frame: measured baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation
measure: Change in N-terminal pro-brain natriuretic peptide
time frame: measured baseline and during follow up visits 3, 6 and 12 months after inclusion or Baroreflex Activation Therapy device activation
intervention type: Device
intervention name: Barostim neo implantation
description: The Barostim neo Implantation is a new promising treatment option for patients with advanced heart failure (HEFrEF) as it might improve cardiac and vascular function by restoring sympathovagal-balance through its effects on the autonomic nervous system.
In this observational study, data from patients who have received the Barostim neo System as part of clinical routine will be collected and analyzed. The implantation of this new device is not part of the study.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Germany
citation: DeMazumder D, Kass DA, O'Rourke B, Tomaselli GF. Cardiac resynchronization therapy restores sympathovagal balance in the failing heart by differential remodeling of cholinergic signaling. Circ Res. 2015 May 8;116(10):1691-9. doi: 10.1161/CIRCRESAHA.116.305268. Epub 2015 Mar 2.
PMID: 25733594
citation: Gronda E, Seravalle G, Trevano FQ, Costantino G, Casini A, Alsheraei A, Lovett EG, Vanoli E, Mancia G, Grassi G. Long-term chronic baroreflex activation: persistent efficacy in patients with heart failure and reduced ejection fraction. J Hypertens. 2015 Aug;33(8):1704-8. doi: 10.1097/HJH.0000000000000603.
PMID: 26132760
citation: Abraham WT, Zile MR, Weaver FA, Butter C, Ducharme A, Halbach M, Klug D, Lovett EG, Muller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Little WC. Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction. JACC Heart Fail. 2015 Jun;3(6):487-496. doi: 10.1016/j.jchf.2015.02.006. Epub 2015 May 14.
PMID: 25982108
citation: Zile MR, Abraham WT, Weaver FA, Butter C, Ducharme A, Halbach M, Klug D, Lovett EG, Muller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Little WC. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy. Eur J Heart Fail. 2015 Oct;17(10):1066-74. doi: 10.1002/ejhf.299. Epub 2015 Jun 10.
PMID: 26011593
citation: Fantoni C, Raffa S, Regoli F, Giraldi F, La Rovere MT, Prentice J, Pastori F, Fratini S, Salerno-Uriarte JA, Klein HU, Auricchio A. Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure. J Am Coll Cardiol. 2005 Nov 15;46(10):1875-82. doi: 10.1016/j.jacc.2005.06.081. Epub 2005 Oct 24.
PMID: 16286175
citation: Oliveira M. Comment on "Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction". Rev Port Cardiol. 2015 Dec;34(12):795-7. doi: 10.1016/j.repce.2015.12.014.
PMID: 27099884
citation: Huang JH, Lin YK, Hsieh MH, Chen SA, Chiu WC, Chen YJ. Modulation of Autonomic Nervous Activity in the Termination of Paroxysmal Atrial Fibrillation. Pacing Clin Electrophysiol. 2017 Apr;40(4):401-408. doi: 10.1111/pace.13045. Epub 2017 Mar 3.
PMID: 28181276
citation: Linz D, Hohl M, Khoshkish S, Mahfoud F, Ukena C, Neuberger HR, Wirth K, Bohm M. Low-Level But Not High-Level Baroreceptor Stimulation Inhibits Atrial Fibrillation in a Pig Model of Sleep Apnea. J Cardiovasc Electrophysiol. 2016 Sep;27(9):1086-92. doi: 10.1111/jce.13020. Epub 2016 Jun 22.
PMID: 27235276
citation: Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger HR, Wirth K, Bohm M. Effects of electrical stimulation of carotid baroreflex and renal denervation on atrial electrophysiology. J Cardiovasc Electrophysiol. 2013 Sep;24(9):1028-33. doi: 10.1111/jce.12171. Epub 2013 May 2.
PMID: 23638844
citation: Dai M, Bao M, Zhang Y, Yu L, Cao Q, Tang Y, Huang H, Wang X, Hu D, Huang C. Low-level carotid baroreflex stimulation suppresses atrial fibrillation by inhibiting left stellate ganglion activity in an acute canine model. Heart Rhythm. 2016 Nov;13(11):2203-2212. doi: 10.1016/j.hrthm.2016.08.021. Epub 2016 Aug 9.
PMID: 27520541
responsible party type: Sponsor
mesh term: Heart Failure
sharing ipd: No