<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/NCT03255057</url>
  </required_header>
  <id_info>
    <org_study_id>HL-CA-5000</org_study_id>
    <nct_id>NCT03255057</nct_id>
  </id_info>
  <brief_title>Extracorporeal CO2 Removal With the Hemolung RAS for Mechanical Ventilation Avoidance During Acute Exacerbation of COPD</brief_title>
  <acronym>VENT-AVOID</acronym>
  <official_title>A Prospective, Multi-Center, Randomized, Controlled, Pivotal Trial to Validate the Safety and Efficacy of the Hemolung® Respiratory Assist System for COPD Patients Experiencing an Acute Exacerbation Requiring Ventilatory Support</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alung Technologies</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alung Technologies</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 study evaluates the safety and efficacy of using the Hemolung RAS to provide low-flow&#xD;
      extracorporeal carbon dioxide removal (ECCO2R) as an alternative or adjunct to invasive&#xD;
      mechanical ventilation for patients who require respiratory support due to an acute&#xD;
      exacerbation of Chronic Obstructive Pulmonary Disease (COPD). It is hypothesized that the&#xD;
      Hemolung RAS can be safely used to avoid or reduce time on invasive mechanical ventilation&#xD;
      compared to COPD patients treated with standard-of-care mechanical ventilation alone.&#xD;
      Eligible patients will be randomized to receive lung support with either the Hemolung RAS&#xD;
      plus standard-of-care mechanical ventilation, or standard-of-care mechanical ventilation&#xD;
      alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Hemolung RAS provides low-flow ECCO2R using a single, 15.5 French dual-lumen catheter&#xD;
      inserted percutaneously in the femoral or jugular vein. Low-flow ECCO2R offers an alternative&#xD;
      or supplement to invasive mechanical ventilation (MV) for patients suffering from acute,&#xD;
      reversible, hypercapnic respiratory failure. In contrast to invasive MV, low-flow ECCO2R&#xD;
      provides partial ventilatory support independently of the lungs. The rationale for this study&#xD;
      is that low-flow ECCO2R with the Hemolung RAS can be used to provide supplemental CO2 removal&#xD;
      in COPD patients experiencing acute hypercapnic respiratory failure to either avoid or reduce&#xD;
      time on invasive MV. In this patient population, avoidance or reduced time on invasive MV may&#xD;
      have significant clinical benefit in reducing the many complications associated with invasive&#xD;
      MV. The major complication risks of low-flow ECCO2R are associated with central venous&#xD;
      catheterization and the need for anticoagulation during treatment. This study is designed to&#xD;
      evaluate the safety and efficacy of Hemolung RAS plus standard-of-care as compared to&#xD;
      standard-of-care alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of enrollment post COVID-19 pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">February 18, 2018</start_date>
  <completion_date type="Actual">August 17, 2022</completion_date>
  <primary_completion_date type="Actual">August 10, 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>Prospective, multi-center, randomized, controlled, two-arm, open-label, adaptive, two-strata, pivotal trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Due to the nature of the interventional device and treatment, the study participants, care providers, and investigators will not be masked. However, an independent Clinical Endpoint Committee will be masked for adjudication of the primary endpoint and serious adverse events. An independent Data and Safety Monitoring Board will make study continuation recommendations based on the statistical analysis plan and the overall safety and efficacy endpoints without masking.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The amount of time in the first five days following randomization that a patient is free of Invasive MV and alive</measure>
    <time_frame>5 days</time_frame>
    <description>Statistically analyzed as Ventilator-Free Days during the 5 days from randomization (VFD-5)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Physiologic benefit</measure>
    <time_frame>Time to extubation from first intubation up to 60 days from randomization</time_frame>
    <description>Based on blood gases and concomitant ventilation parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Avoidance of intubation</measure>
    <time_frame>Within 60 days from randomization</time_frame>
    <description>Incidence of subjects who did not require intubation at any time during their primary hospital admission for the exacerbation for which they were enrolled in the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ability to communicate by speaking</measure>
    <time_frame>Randomization to end of treatment or 14 days, whichever is sooner</time_frame>
    <description>Number of days from randomization to end of treatment (end of Invasive MV in Control Arm and end of Hemolung treatment in Investigational Arm) subject is able to communicate by speaking</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ability to eat and drink orally</measure>
    <time_frame>Randomization to end of treatment or 14 days, whichever is sooner</time_frame>
    <description>Number of days from randomization to end of treatment (end of Invasive MV in Control Arm and end of Hemolung treatment in Investigational Arm) subject is able to eat and drink orally</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU Mobility</measure>
    <time_frame>Randomization to end of treatment or 14 days, whichever is sooner</time_frame>
    <description>Ability of subject to mobilize in bed and out of bed while in Intensive Care as assessed using ICU Mobility Score (IMS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily dose of sedatives, analgesics, and paralytics while in ICU</measure>
    <time_frame>From randomization to ICU discharge up to 60 days from randomization</time_frame>
    <description>A qualify of life measure for subjects while in ICU measured by reported concomitant medications while in ICU.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of new tracheotomies</measure>
    <time_frame>Within 60 days from randomization</time_frame>
    <description>Incidence of new tracheotomies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Within 60 days from randomization</time_frame>
    <description>All Serious Adverse Events (SAE) from randomization to 60 days and non-serious adverse events from randomization to ICU discharge or 30 days, whichever is sooner (adjudicated by the Clincal Events Committee)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause in-hospital mortality</measure>
    <time_frame>Within 60 days from randomization</time_frame>
    <description>Subject death from any cause while still admitted to hospital for the acute exacerbation for which they were enrolled in the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause (health-related) mortality at 60 days from randomization</measure>
    <time_frame>Within 60 days from randomization</time_frame>
    <description>Incidence of health-related deaths at 60 days from randomization, regardless of subject location at time of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of failed extubations</measure>
    <time_frame>Within 60 days from randomization</time_frame>
    <description>Incidence of re-intubation within 48 hours of extubation for original exacerbation</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Time to ICU discharge</measure>
    <time_frame>From ICU admission to discharge up to 60 days from randomization</time_frame>
    <description>Time from ICU admission to ICU discharge for initial exacerbation for which the subject was enrolled for subjects surviving to discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to hospital discharge</measure>
    <time_frame>From hospital admission to discharge up to 60 days from randomization</time_frame>
    <description>Time from hospital admission to hospital discharge for initial exacerbation for which the subject was enrolled for subjects surviving to discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Time on ventilatory support</measure>
    <time_frame>Randomization to end of Hemolung an Invasive MV for initial exacerbation up to 60 days from randomization</time_frame>
    <description>Total time on Hemolung and/or Invasive MV support for initial exacerbation</description>
  </other_outcome>
  <other_outcome>
    <measure>VFD-30</measure>
    <time_frame>Randomization to Day 30</time_frame>
    <description>Ventilator-free days from randomization to 30 days from randomization</description>
  </other_outcome>
  <other_outcome>
    <measure>SOFA Score</measure>
    <time_frame>From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days</time_frame>
    <description>Sequential Organ Failure Assessment Score from randomization to 24 hours after end of treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>Dyspnea</measure>
    <time_frame>From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days</time_frame>
    <description>A quality of life measure for subjects while in ICU measured with a Visual Analog Score</description>
  </other_outcome>
  <other_outcome>
    <measure>ICU Delirium</measure>
    <time_frame>From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days</time_frame>
    <description>A quality of life measure for subjects while in ICU measured with the Confusion Assessment Measure for ICU (CAM-ICU) score</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of DNI/DNR/Comfort care requests post-randomization</measure>
    <time_frame>From randomization to 60 days from randomizaiton</time_frame>
    <description>Incidence of DNI/DNR/Comfort care requests post-randomization</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of hospital readmissions</measure>
    <time_frame>From randomization to 60 days from randomizaiton</time_frame>
    <description>Number of new hospital admissions after hospital discharge for original exacerbation</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">113</enrollment>
  <condition>Acute Exacerbation of COPD</condition>
  <arm_group>
    <arm_group_label>Hemolung plus SOC IMV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low-flow ECCO2R with the Hemolung Respiratory Assist System as an alternative or adjunct to standard-of-care (SOC) invasive mechanical ventilation (IMV)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SOC IMV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard-of-care (SOC) invasive mechanical ventilation (IMV) alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Hemolung Respiratory Assist System</intervention_name>
    <description>Treatment with a medical device called the Hemolung RAS. The Hemolung RAS includes three components: the Hemolung Controller, the Hemolung Cartridge, and the Hemolung Catheter. The intervention is use of the Hemolung RAS to provide partial lung support for acute hypercapnic lung failure by filtering carbon dioxide from venous blood using a central venous catheter through which venous blood is pumped at flows of 350-550 milliliters per minute to and from an external circuit containing a hollow fiber membrane blood gas exchanger (with heparin-coated fibers) integrated with a centrifugal pump.</description>
    <arm_group_label>Hemolung plus SOC IMV</arm_group_label>
    <other_name>Low-flow extracorporeal carbon dioxide removal</other_name>
    <other_name>ECCO2R</other_name>
    <other_name>Hemolung RAS</other_name>
    <other_name>Hemolung</other_name>
    <other_name>Respiratory dialysis</other_name>
    <other_name>Lung dialysis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Invasive mechanical ventilation</intervention_name>
    <description>Lung support for acute lung failure applied with a mechanical ventilation device that uses positive pressure to mechanically inflate the lungs and facilitate exhalation via an endotracheal tube or tracheotomy.</description>
    <arm_group_label>Hemolung plus SOC IMV</arm_group_label>
    <arm_group_label>SOC IMV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 40 years&#xD;
&#xD;
          2. Confirmed diagnosis of underlying COPD or ACOS (Asthma-COPD Overlap Syndrome)&#xD;
&#xD;
          3. Experiencing acute hypercapnic respiratory failure&#xD;
&#xD;
          4. Informed consent from patient or legally authorized representative&#xD;
&#xD;
          5. Meets one of the three following criteria:&#xD;
&#xD;
               1. Is at high risk of requiring intubation and invasive mechanical ventilation (MV)&#xD;
                  after at least one hour on NIV due to one or more of the following:&#xD;
&#xD;
                    -  Respiratory acidosis (arterial pH &lt;= 7.25) despite NIV&#xD;
&#xD;
                    -  Worsening hypercapnia or respiratory acidosis relative to baseline blood&#xD;
                       gases&#xD;
&#xD;
                    -  No improvement in PaCO2 relative to baseline blood gases and presence of&#xD;
                       moderate or severe dyspnea&#xD;
&#xD;
                    -  Presence of tachypnea &gt; 30 breaths per minute&#xD;
&#xD;
                    -  Intolerance of NIV with failure to improve or worsening acidosis, dyspnea or&#xD;
                       work of breathing&#xD;
&#xD;
                  *OR*&#xD;
&#xD;
               2. After starting NIV with a baseline arterial pH ≤ 7.25, shows signs of progressive&#xD;
                  clinical decompensation manifested by decreased mental capacity, inability to&#xD;
                  tolerate NIV, or increased or decreased respiratory rate in setting of worsened&#xD;
                  or unchanged acidosis.&#xD;
&#xD;
                  *OR*&#xD;
&#xD;
               3. Currently intubated and receiving Invasive MV, meeting both of the following:&#xD;
&#xD;
                    -  Intubated for ≤ 5 days (from intubation to time of consent), AND&#xD;
&#xD;
                    -  Has failed a spontaneous breathing trial OR is deemed not suitable for a&#xD;
                       spontaneous breathing trial (SBT) OR is deemed not suitable for extubation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. DNR/DNI order&#xD;
&#xD;
          2. Hemodynamic instability (mean arterial pressure &lt; 60 mmHg) despite infusion of&#xD;
             vasoactive drugs&#xD;
&#xD;
          3. Acute coronary syndrome&#xD;
&#xD;
          4. Current presence of severe pulmonary edema due to Congestive Heart Failure&#xD;
&#xD;
          5. PaO2/FiO2 &lt; 120 mmHg on PEEP &gt;/= 5 cmH2O&#xD;
&#xD;
          6. Presence of bleeding diathesis or other contraindication to anticoagulation therapy&#xD;
&#xD;
          7. Platelet count &gt;= 100,000/mm3 not requiring daily transfusions to maintain platelet&#xD;
             count above 100,000/mm3 at time of screening&#xD;
&#xD;
          8. Hemoglobin &gt;= 7.0 gm% not requiring daily transfusions to maintain hemoglobin count&#xD;
             above 7.0 gm% at time of screening, and no active major bleeding&#xD;
&#xD;
          9. Unable to protect airway (e.g. unable to generate cough or clear secretions) or&#xD;
             significant weakness or paralysis of respiratory muscles due to causes unrelated to&#xD;
             acute exacerbation of COPD&#xD;
&#xD;
         10. Cerebrovascular accident, intracranial bleed, head injury or other neurological&#xD;
             disorder likely to adversely affect ventilation or airway protection.&#xD;
&#xD;
         11. Hypersensitivity to heparin or history of previous heparin-induced thrombocytopenia&#xD;
             (HIT Type II)&#xD;
&#xD;
         12. Presence of a significant pneumothorax or bronchopleural fistula&#xD;
&#xD;
         13. Current uncontrolled, major psychiatric disorder&#xD;
&#xD;
         14. Current participation in any other interventional clinical study&#xD;
&#xD;
         15. Pregnant women (women of child bearing potential require a pregnancy test)&#xD;
&#xD;
         16. Neutropenic (absolute neutrophil count &lt; 1,00mm3, not transient) related to the&#xD;
             presence or treatment of a malignancy; recent bone marrow transplant (within prior 8&#xD;
             months); current, uncontrolled AIDS.&#xD;
&#xD;
         17. Fulminant liver failure&#xD;
&#xD;
         18. Known vascular abnormality or condition which could complicate or prevent successful&#xD;
             Hemolung Catheter insertion&#xD;
&#xD;
         19. Terminal patients not expected to survive current hospitalization&#xD;
&#xD;
         20. Requiring continuous home ventilation via a tracheostomyy&#xD;
&#xD;
         21. Any disease or condition that, in the judgment of the investigator, either places the&#xD;
             subject at undue risk of complications from the Hemolung RAS device, or may reduce the&#xD;
             subject's likelihood of benefitting from therapy with the Hemolung RASr&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicholas Hill, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tufts University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UC Davis Medical Group</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Denver Health Medical Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care Health System</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida - Health Shands</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>WellStar Kennestone Regional Medical Center</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lexington VA Healthcare</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40502</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>LSU Health Shreveport</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health Hospitals</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minneapolis Heart</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers-Robert Wood Johnson University Hospital</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albany Medical Center</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208-3412</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwell Health</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Presbyterian Hospital/Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</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>Lehigh Valley Health Network</name>
      <address>
        <city>Allentown</city>
        <state>Pennsylvania</state>
        <zip>18103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital of University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Temple University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Erlanger</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memphis VA Medical Center</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT McGovern Medical School Memorial Hermann</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott and White Memorial Hospital</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Medical Center</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Health Care Services</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Burki NK, Mani RK, Herth FJF, Schmidt W, Teschler H, Bonin F, Becker H, Randerath WJ, Stieglitz S, Hagmeyer L, Priegnitz C, Pfeifer M, Blaas SH, Putensen C, Theuerkauf N, Quintel M, Moerer O. A novel extracorporeal CO(2) removal system: results of a pilot study of hypercapnic respiratory failure in patients with COPD. Chest. 2013 Mar;143(3):678-686. doi: 10.1378/chest.12-0228.</citation>
    <PMID>23460154</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>October 13, 2022</last_update_submitted>
  <last_update_submitted_qc>October 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT03255057
org study id: HL-CA-5000
nct id: NCT03255057
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
This study evaluates the safety and efficacy of using the Hemolung RAS to provide low-flow
      extracorporeal carbon dioxide removal (ECCO2R) as an alternative or adjunct to invasive
      mechanical ventilation for patients who require respiratory support due to an acute
      exacerbation of Chronic Obstructive Pulmonary Disease (COPD). It is hypothesized that the
      Hemolung RAS can be safely used to avoid or reduce time on invasive mechanical ventilation
      compared to COPD patients treated with standard-of-care mechanical ventilation alone.
      Eligible patients will be randomized to receive lung support with either the Hemolung RAS
      plus standard-of-care mechanical ventilation, or standard-of-care mechanical ventilation
      alone.
The Hemolung RAS provides low-flow ECCO2R using a single, 15.5 French dual-lumen catheter
      inserted percutaneously in the femoral or jugular vein. Low-flow ECCO2R offers an alternative
      or supplement to invasive mechanical ventilation (MV) for patients suffering from acute,
      reversible, hypercapnic respiratory failure. In contrast to invasive MV, low-flow ECCO2R
      provides partial ventilatory support independently of the lungs. The rationale for this study
      is that low-flow ECCO2R with the Hemolung RAS can be used to provide supplemental CO2 removal
      in COPD patients experiencing acute hypercapnic respiratory failure to either avoid or reduce
      time on invasive MV. In this patient population, avoidance or reduced time on invasive MV may
      have significant clinical benefit in reducing the many complications associated with invasive
      MV. The major complication risks of low-flow ECCO2R are associated with central venous
      catheterization and the need for anticoagulation during treatment. This study is designed to
      evaluate the safety and efficacy of Hemolung RAS plus standard-of-care as compared to
      standard-of-care alone.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, multi-center, randomized, controlled, two-arm, open-label, adaptive, two-strata, pivotal trial
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Due to the nature of the interventional device and treatment, the study participants, care providers, and investigators will not be masked. However, an independent Clinical Endpoint Committee will be masked for adjudication of the primary endpoint and serious adverse events. An independent Data and Safety Monitoring Board will make study continuation recommendations based on the statistical analysis plan and the overall safety and efficacy endpoints without masking.
measure: The amount of time in the first five days following randomization that a patient is free of Invasive MV and alive
time frame: 5 days
description: Statistically analyzed as Ventilator-Free Days during the 5 days from randomization (VFD-5)
measure: Physiologic benefit
time frame: Time to extubation from first intubation up to 60 days from randomization
description: Based on blood gases and concomitant ventilation parameters
measure: Avoidance of intubation
time frame: Within 60 days from randomization
description: Incidence of subjects who did not require intubation at any time during their primary hospital admission for the exacerbation for which they were enrolled in the study.
measure: Ability to communicate by speaking
time frame: Randomization to end of treatment or 14 days, whichever is sooner
description: Number of days from randomization to end of treatment (end of Invasive MV in Control Arm and end of Hemolung treatment in Investigational Arm) subject is able to communicate by speaking
measure: Ability to eat and drink orally
time frame: Randomization to end of treatment or 14 days, whichever is sooner
description: Number of days from randomization to end of treatment (end of Invasive MV in Control Arm and end of Hemolung treatment in Investigational Arm) subject is able to eat and drink orally
measure: ICU Mobility
time frame: Randomization to end of treatment or 14 days, whichever is sooner
description: Ability of subject to mobilize in bed and out of bed while in Intensive Care as assessed using ICU Mobility Score (IMS)
measure: Daily dose of sedatives, analgesics, and paralytics while in ICU
time frame: From randomization to ICU discharge up to 60 days from randomization
description: A qualify of life measure for subjects while in ICU measured by reported concomitant medications while in ICU.
measure: Incidence of new tracheotomies
time frame: Within 60 days from randomization
description: Incidence of new tracheotomies
measure: Adverse events
time frame: Within 60 days from randomization
description: All Serious Adverse Events (SAE) from randomization to 60 days and non-serious adverse events from randomization to ICU discharge or 30 days, whichever is sooner (adjudicated by the Clincal Events Committee)
measure: All-cause in-hospital mortality
time frame: Within 60 days from randomization
description: Subject death from any cause while still admitted to hospital for the acute exacerbation for which they were enrolled in the study.
measure: All-cause (health-related) mortality at 60 days from randomization
time frame: Within 60 days from randomization
description: Incidence of health-related deaths at 60 days from randomization, regardless of subject location at time of death.
measure: Incidence of failed extubations
time frame: Within 60 days from randomization
description: Incidence of re-intubation within 48 hours of extubation for original exacerbation
measure: Time to ICU discharge
time frame: From ICU admission to discharge up to 60 days from randomization
description: Time from ICU admission to ICU discharge for initial exacerbation for which the subject was enrolled for subjects surviving to discharge
measure: Time to hospital discharge
time frame: From hospital admission to discharge up to 60 days from randomization
description: Time from hospital admission to hospital discharge for initial exacerbation for which the subject was enrolled for subjects surviving to discharge
measure: Time on ventilatory support
time frame: Randomization to end of Hemolung an Invasive MV for initial exacerbation up to 60 days from randomization
description: Total time on Hemolung and/or Invasive MV support for initial exacerbation
measure: VFD-30
time frame: Randomization to Day 30
description: Ventilator-free days from randomization to 30 days from randomization
measure: SOFA Score
time frame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
description: Sequential Organ Failure Assessment Score from randomization to 24 hours after end of treatment
measure: Dyspnea
time frame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
description: A quality of life measure for subjects while in ICU measured with a Visual Analog Score
measure: ICU Delirium
time frame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
description: A quality of life measure for subjects while in ICU measured with the Confusion Assessment Measure for ICU (CAM-ICU) score
measure: Incidence of DNI/DNR/Comfort care requests post-randomization
time frame: From randomization to 60 days from randomizaiton
description: Incidence of DNI/DNR/Comfort care requests post-randomization
measure: Incidence of hospital readmissions
time frame: From randomization to 60 days from randomizaiton
description: Number of new hospital admissions after hospital discharge for original exacerbation
arm group label: Hemolung plus SOC IMV
arm group type: Experimental
description: Low-flow ECCO2R with the Hemolung Respiratory Assist System as an alternative or adjunct to standard-of-care (SOC) invasive mechanical ventilation (IMV)
arm group label: SOC IMV
arm group type: Active Comparator
description: Standard-of-care (SOC) invasive mechanical ventilation (IMV) alone
intervention type: Device
intervention name: Hemolung Respiratory Assist System
description: Treatment with a medical device called the Hemolung RAS. The Hemolung RAS includes three components: the Hemolung Controller, the Hemolung Cartridge, and the Hemolung Catheter. The intervention is use of the Hemolung RAS to provide partial lung support for acute hypercapnic lung failure by filtering carbon dioxide from venous blood using a central venous catheter through which venous blood is pumped at flows of 350-550 milliliters per minute to and from an external circuit containing a hollow fiber membrane blood gas exchanger (with heparin-coated fibers) integrated with a centrifugal pump.
arm group label: Hemolung plus SOC IMV
other name: Low-flow extracorporeal carbon dioxide removal
other name: ECCO2R
other name: Hemolung RAS
other name: Hemolung
other name: Respiratory dialysis
other name: Lung dialysis
intervention type: Device
intervention name: Invasive mechanical ventilation
description: Lung support for acute lung failure applied with a mechanical ventilation device that uses positive pressure to mechanically inflate the lungs and facilitate exhalation via an endotracheal tube or tracheotomy.
arm group label: Hemolung plus SOC IMV
arm group label: SOC IMV
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Nicholas Hill, MD
role: Principal Investigator
affiliation: Tufts University Medical Center
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country: United States
citation: Burki NK, Mani RK, Herth FJF, Schmidt W, Teschler H, Bonin F, Becker H, Randerath WJ, Stieglitz S, Hagmeyer L, Priegnitz C, Pfeifer M, Blaas SH, Putensen C, Theuerkauf N, Quintel M, Moerer O. A novel extracorporeal CO(2) removal system: results of a pilot study of hypercapnic respiratory failure in patients with COPD. Chest. 2013 Mar;143(3):678-686. doi: 10.1378/chest.12-0228.
PMID: 23460154
responsible party type: Sponsor