<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/NCT03783884</url>
  </required_header>
  <id_info>
    <org_study_id>P-300</org_study_id>
    <nct_id>NCT03783884</nct_id>
  </id_info>
  <brief_title>A Protocol Comparing Temporary Transvenous Diaphragm Pacing to Standard of Care for Weaning From Mechanical Ventilation</brief_title>
  <acronym>RESCUE3</acronym>
  <official_title>A Randomized, Controlled, Open-labeled, Multi-center Clinical Trial to Evaluate the Safe and Effective Performance of the Lungpacer Diaphragm Pacing Therapy System in Patients Who Have Failed to Wean From Mechanical Ventilation.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lungpacer Medical Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lungpacer Medical Inc.</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_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical investigation is an open-label, multi-center RCT to demonstrate the safety and&#xD;
      effective performance of the Lungpacer DPTS (plus standard of care) as compared to Control&#xD;
      (standard of care only) in patients aged 18 years or older who are receiving mechanical&#xD;
      ventilation. Eligible Subjects will have received mechanical ventilation for ≥96 hours (4&#xD;
      days) and failed two weaning attempts.&#xD;
&#xD;
      The goal or outcome is to show a numerically greater proportion of subjects weaned in the&#xD;
      Treatment (Lungpacer DPTS) group as compared to the Control group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The intended patient population is applicable for Lungpacer DPT because there are no&#xD;
      noninvasive alternative treatments for patients who are difficult to wean from MV (i.e., ≥96&#xD;
      hours (4 days) on MV) or who have required prolonged MV (&gt;7 days). The intended patient&#xD;
      population includes approximately one-third of all patients on mechanical ventilation. Under&#xD;
      standard of care, approximately 50% of these patients will recover from mechanical&#xD;
      ventilation (Jung, 2016). Standard of care involves daily weaning attempts, known as&#xD;
      Spontaneous Breathing Trials (SBTs) or Ventilator Liberation Trials (VLTs) that are intended&#xD;
      to encourage diaphragm use and strengthening over time.Therefore, Lungpacer DPT efficacy&#xD;
      evaluation must be compared to standard of care in a Control group. Lack of recovery from&#xD;
      mechanical ventilation may be due to the inability of a patient to participate in VLTs or&#xD;
      weaning attempts, due to extensive diaphragm weakness or sedation, the inability of VLTs to&#xD;
      induce sufficient diaphragm strengthening, or co-morbidities that prevent recovery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low enrollment rate.&#xD;
  </why_stopped>
  <start_date type="Actual">June 14, 2019</start_date>
  <completion_date type="Actual">January 27, 2023</completion_date>
  <primary_completion_date type="Actual">December 28, 2022</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>1:1 randomization of treatment and control group</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Successful wean</measure>
    <time_frame>30 days</time_frame>
    <description>The proportion of subjects who are successfully weaned will be statistically significantly greater for subjects randomized to Treatment (Lungpacer DPTS) compared to subjects randomized to Control.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximal Inspiratory Pressure mean change</measure>
    <time_frame>30 days</time_frame>
    <description>The MIP mean change from baseline will be statistically significantly greater for subjects randomized to Lungpacer DPTS compared to subjects randomized to Control.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Rapid Shallow Breathing Index (RSBI)</measure>
    <time_frame>30 days</time_frame>
    <description>Change in RSBI over time from randomization (baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>30 days</time_frame>
    <description>To compare Treatment (Lungpacer DPTS) subjects to Control subjects for Day 30 mortality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of RSBI Change</measure>
    <time_frame>30 days</time_frame>
    <description>Rate of RSBI change per day from randomization (baseline) to last available measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of MIP Change</measure>
    <time_frame>30 days</time_frame>
    <description>Rate of MIP change per day from randomization (baseline) to last available measure;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in MIP</measure>
    <time_frame>30 days</time_frame>
    <description>Change in MIP over time from randomization (baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days on MV</measure>
    <time_frame>Successful weaning or day 30</time_frame>
    <description>Days on mechanical ventilation from Day 1 to removal from MV associated with successful weaning or Day 30, whichever comes first.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse Event Assessment</measure>
    <time_frame>30 days</time_frame>
    <description>Adverse events for subjects randomized to Treatment (Lungpacer DPTS) as compared to subjects randomized to Control.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">223</enrollment>
  <condition>Ventilator Induced Diaphragm Dysfunction</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subject receives Lungpacer Catheter for transvenous phrenic nerve stimulation to deliver Diaphragm Pacing Therapy Sessions. DPT sessions are 6 sets of 10, delivered twice daily, for a total of 120 stimulation reps per day, plus standard of care for weaning from mechanical ventilation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subject does not receive Lungpacer Catheter or DPT. Subject receives only Standard of care for weaning from mechanical ventilation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Lungpacer Diaphragm Pacing Therapy</intervention_name>
    <description>Transvenous phrenic nerve stimulation to induce diaphragm contraction.</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>Lungpacer DPTS</other_name>
    <other_name>AeroPace System</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Are 18 years or older, and,&#xD;
&#xD;
          2. Have been mechanically ventilated for ≥96 hours (4 days), and,&#xD;
&#xD;
          3. Have satisfied the Readiness-to-Wean criteria, and,&#xD;
&#xD;
          4. Have failed at least 2 weaning attempts (that were conducted at least 48 hours after&#xD;
             initiation of MV, and, that were conducted on different calendar days, and, at least&#xD;
             one of which was the protocol-specific Ventilator Liberation Trial).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. MIP (absolute value) &gt;50 cm H2O;&#xD;
&#xD;
          2. Invasive mechanical ventilation &gt;90 days;&#xD;
&#xD;
          3. Currently on ECMO;&#xD;
&#xD;
          4. Weaning failure due to hypervolemia;&#xD;
&#xD;
          5. Medical history (including imaging) or known anatomy that prevents percutaneous&#xD;
             insertion of the Catheter into the intended thoracic vein on the left side.&#xD;
&#xD;
          6. Clinically overt congestive heart failure that is preventing weaning;&#xD;
&#xD;
          7. Currently being treated with neuromuscular blockade;&#xD;
&#xD;
          8. Pre-existing neurological, neuromuscular or muscular disorder that could affect the&#xD;
             respiratory muscles;&#xD;
&#xD;
          9. Pre-existing severe chronic pulmonary fibrosis;&#xD;
&#xD;
         10. Pleural effusions occupying greater than one third of the pleural space on either&#xD;
             side;&#xD;
&#xD;
         11. BMI &gt;45 kg/m2;&#xD;
&#xD;
         12. Known or suspected phrenic nerve paralysis;&#xD;
&#xD;
         13. Any electrical device (implanted or external) that may be prone to interaction with,&#xD;
             or interference from the Lungpacer DPTS including neurological pacing/stimulator&#xD;
             devices, cardiac pacemakers and defibrillators;&#xD;
&#xD;
         14. Current hemodynamic instability, sepsis or septic shock;&#xD;
&#xD;
         15. Prior bacteremia reported within the last 48 hours;&#xD;
&#xD;
         16. Anticipating withdrawal of life support and/or shift to palliation as the goal of&#xD;
             care;&#xD;
&#xD;
         17. Known or suspected to be pregnant or lactating;&#xD;
&#xD;
         18. Currently being treated in another clinical trial studying an experimental treatment&#xD;
             that could affect the study primary outcome.&#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>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Anschutz Medical Campus</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida, Shands</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edward Hines VA Hospital</name>
      <address>
        <city>Hines</city>
        <state>Illinois</state>
        <zip>60141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Health Methodist Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Hospital and Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minneapolis Heart Institute Foundation</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Health Creighton University Medical Center - Bergan Mercy</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Englewood Hospital Medical Center</name>
      <address>
        <city>Englewood</city>
        <state>New Jersey</state>
        <zip>07631</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Temple University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kent County Memorial Hospital</name>
      <address>
        <city>Warwick</city>
        <state>Rhode Island</state>
        <zip>02886</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Baptist Hospital</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern, Zale Lipshy Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital La Pitié-Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <zip>67091</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Greifswald</name>
      <address>
        <city>Greifswald</city>
        <state>Mecklenburg-Vorpommern</state>
        <zip>17475</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Berlin Charite Mitte</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KEM Essen</name>
      <address>
        <city>Essen</city>
        <zip>45276</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SLK Löwenstein</name>
      <address>
        <city>Löwenstein</city>
        <zip>74245</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nürnberg Klinikum Nord</name>
      <address>
        <city>Nürnberg</city>
        <zip>90419</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FKKG Schmallenberg</name>
      <address>
        <city>Schmallenberg</city>
        <zip>57392</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Solingen Krankenhaus Bethanien</name>
      <address>
        <city>Solingen</city>
        <zip>42699</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://lungpacer.com</url>
    <description>Sponsor website</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>VIDD</keyword>
  <keyword>Diaphragm Atrophy</keyword>
  <keyword>Weaning Failure</keyword>
  <keyword>VLT</keyword>
  <keyword>SBT</keyword>
  <keyword>VILI</keyword>
  <keyword>Phrenic Nerve Stimulation</keyword>
  <keyword>Maximal Inspiratory Pressure</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Only investigators participating in this clinical trial will be able to see final de-identified participant data at the completion of the study.</ipd_description>
  </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/NCT03783884
org study id: P-300
nct id: NCT03783884
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
This clinical investigation is an open-label, multi-center RCT to demonstrate the safety and
      effective performance of the Lungpacer DPTS (plus standard of care) as compared to Control
      (standard of care only) in patients aged 18 years or older who are receiving mechanical
      ventilation. Eligible Subjects will have received mechanical ventilation for ≥96 hours (4
      days) and failed two weaning attempts.

      The goal or outcome is to show a numerically greater proportion of subjects weaned in the
      Treatment (Lungpacer DPTS) group as compared to the Control group.
The intended patient population is applicable for Lungpacer DPT because there are no
      noninvasive alternative treatments for patients who are difficult to wean from MV (i.e., ≥96
      hours (4 days) on MV) or who have required prolonged MV (>7 days). The intended patient
      population includes approximately one-third of all patients on mechanical ventilation. Under
      standard of care, approximately 50% of these patients will recover from mechanical
      ventilation (Jung, 2016). Standard of care involves daily weaning attempts, known as
      Spontaneous Breathing Trials (SBTs) or Ventilator Liberation Trials (VLTs) that are intended
      to encourage diaphragm use and strengthening over time.Therefore, Lungpacer DPT efficacy
      evaluation must be compared to standard of care in a Control group. Lack of recovery from
      mechanical ventilation may be due to the inability of a patient to participate in VLTs or
      weaning attempts, due to extensive diaphragm weakness or sedation, the inability of VLTs to
      induce sufficient diaphragm strengthening, or co-morbidities that prevent recovery.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 1:1 randomization of treatment and control group
primary purpose: Treatment
masking: None (Open Label)
measure: Successful wean
time frame: 30 days
description: The proportion of subjects who are successfully weaned will be statistically significantly greater for subjects randomized to Treatment (Lungpacer DPTS) compared to subjects randomized to Control.
measure: Maximal Inspiratory Pressure mean change
time frame: 30 days
description: The MIP mean change from baseline will be statistically significantly greater for subjects randomized to Lungpacer DPTS compared to subjects randomized to Control.
measure: Change in Rapid Shallow Breathing Index (RSBI)
time frame: 30 days
description: Change in RSBI over time from randomization (baseline)
measure: Mortality
time frame: 30 days
description: To compare Treatment (Lungpacer DPTS) subjects to Control subjects for Day 30 mortality.
measure: Rate of RSBI Change
time frame: 30 days
description: Rate of RSBI change per day from randomization (baseline) to last available measure
measure: Rate of MIP Change
time frame: 30 days
description: Rate of MIP change per day from randomization (baseline) to last available measure;
measure: Change in MIP
time frame: 30 days
description: Change in MIP over time from randomization (baseline)
measure: Days on MV
time frame: Successful weaning or day 30
description: Days on mechanical ventilation from Day 1 to removal from MV associated with successful weaning or Day 30, whichever comes first.
measure: Adverse Event Assessment
time frame: 30 days
description: Adverse events for subjects randomized to Treatment (Lungpacer DPTS) as compared to subjects randomized to Control.
arm group label: Treatment
arm group type: Active Comparator
description: Subject receives Lungpacer Catheter for transvenous phrenic nerve stimulation to deliver Diaphragm Pacing Therapy Sessions. DPT sessions are 6 sets of 10, delivered twice daily, for a total of 120 stimulation reps per day, plus standard of care for weaning from mechanical ventilation.
arm group label: Control
arm group type: No Intervention
description: Subject does not receive Lungpacer Catheter or DPT. Subject receives only Standard of care for weaning from mechanical ventilation.
intervention type: Device
intervention name: Lungpacer Diaphragm Pacing Therapy
description: Transvenous phrenic nerve stimulation to induce diaphragm contraction.
arm group label: Treatment
other name: Lungpacer DPTS
other name: AeroPace System
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: France
country: Germany
country: United States
url: http://lungpacer.com
description: Sponsor website
responsible party type: Sponsor
sharing ipd: No
ipd description: Only investigators participating in this clinical trial will be able to see final de-identified participant data at the completion of the study.