<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/NCT01721434</url>
  </required_header>
  <id_info>
    <org_study_id>Levo2</org_study_id>
    <nct_id>NCT01721434</nct_id>
  </id_info>
  <brief_title>Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients</brief_title>
  <official_title>Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Nijmegen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Orion Corporation, Orion Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Medical Center Nijmegen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Levosimendan is a relatively new drug that improves cardiac contractility in patients with&#xD;
      heart failure. Its main mechanism of action is enhanced binding of calcium to the myocardial&#xD;
      contractile proteins. Recent data from our lab showed that levosimendan improves&#xD;
      contractility of human diaphragm in vitro (muscle fibers from COPD patient diaphragm) and in&#xD;
      vivo (healthy subjects). Accordingly, levosimendan may appear of value in the treatment of&#xD;
      disorders associated with impaired respiratory muscle function, such as mechanically&#xD;
      ventilated patients.We hypothesize that levosimendan could improve respiratory muscle&#xD;
      function in mechanically ventilated patients commencing a CPAP trial.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">May 2016</completion_date>
  <primary_completion_date type="Anticipated">May 2016</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neuro-mechanical efficiency of the diaphragm</measure>
    <time_frame>Artefact-free periode in the last 10 minutes of each CPAP trial</time_frame>
    <description>The primary outcome measure is the neuro-mechanical efficiency(i.e. the ratio of diaphragm electrical activity and transdiaphragmatic pressure) of the diaphragm during a continuous positive airway pressure (CPAP) trial.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neuro-ventilatory efficiency of the diaphragm</measure>
    <time_frame>Artefact-free periode in the last 10 minutes of each CPAP trial</time_frame>
    <description>A secondary outcome measure is the neuro-ventilatory efficiency (i.e. the ratio of diaphragm electrical activity and tidal volume) during a continuous positive airway pressure (CPAP) trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen consumption (VO2)</measure>
    <time_frame>Artefact-free periode in the last 10 minutes of each CPAP trial</time_frame>
    <description>A secondary outcome measure is the oxygen consumption during a continuous positive airway pressure (CPAP) trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial pressure of oxygen in arterial blood (PaO2)</measure>
    <time_frame>Last minute of the 30 minute CPAP trial</time_frame>
    <description>A secondary outcome measure is the PaO2 at the end of a continuous positive airway pressure (CPAP) trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accessory respiratory muscle activity</measure>
    <time_frame>Measured during a one hour protocol after the second CPAP trial.</time_frame>
    <description>To determine the effects of levosimendan on accessory respiratory muscle function, ventilator settings are adapted after the last CPAP-trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Carbon dioxide production (VCO2)</measure>
    <time_frame>Artefact-free periode in the last 10 minutes of each CPAP trial</time_frame>
    <description>A secondary outcome measure is the carbon dioxide production during a continuous positive airway pressure (CPAP) trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial pressure of carbon dioxide in arterial blood (PaCO2)</measure>
    <time_frame>Last minute of the 30 minute CPAP trial</time_frame>
    <description>A secondary outcome measure is the PaCO2 at the and of a continuous positive airway pressure (CPAP) trial.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">42</enrollment>
  <condition>Muscle Weakness Conditions</condition>
  <condition>Weaning Failure</condition>
  <arm_group>
    <arm_group_label>Levosimendan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Levosimendan 0.2 ug/kg/min intravenous for a single 7 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Similar coloured placebo intravenous for a single 7 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levosimendan</intervention_name>
    <arm_group_label>Levosimendan</arm_group_label>
    <other_name>Simdax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Similar coloured placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  mechanical ventilation &gt; 3 days&#xD;
&#xD;
          -  informed consent&#xD;
&#xD;
          -  able to sustain a CPAP trial for 30 minutes&#xD;
&#xD;
          -  PaO2/FiO2 ratio &gt; 200 mmHg&#xD;
&#xD;
          -  ventilatory settings: positive end expiratory pressure &lt;= 10 cmH2O, pressure support&#xD;
             &lt;= 10 cmH2O&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pre-existent muscle disease (congenital or acquired) or diseases/disorders known to be&#xD;
             associated with myopathy including auto-immune diseases&#xD;
&#xD;
          -  pre-existent cardiac disease (based on history, electrocardiography and transthoracic&#xD;
             echocardiography)&#xD;
&#xD;
          -  upper airway/esophageal pathology (i.e. recent surgery, esophageal varices,&#xD;
             diaphragmatic hernia)&#xD;
&#xD;
          -  phrenic nerve lesions&#xD;
&#xD;
          -  pregnancy, breast feeding&#xD;
&#xD;
          -  severe renal failure (serum creatinine &gt; 150 umol/L)&#xD;
&#xD;
          -  severe hepatic failure&#xD;
&#xD;
          -  recent (within 5 days) nasal bleeding&#xD;
&#xD;
          -  systolic blood pressure &lt; 120 mmHg&#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>Leo Heunks, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Leo MA Heunks, MD, PhD</last_name>
    <phone>024-3617273</phone>
    <email>l.heunks@ic.umcn.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jonne Doorduin, MSc</last_name>
    <phone>024-3617273</phone>
    <email>j.doorduin@ic.umcn.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Radboud University Nijmegen Medical Centre</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6500HB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Leo MA Heunks, MD, PhD</last_name>
      <phone>024-3617273</phone>
      <email>l.heunks@ic.umcn.nl</email>
    </contact>
    <contact_backup>
      <last_name>Jonne Doorduin, MSc</last_name>
      <phone>024-3617273</phone>
      <email>j.doorduin@ic.umcn.nl</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>September 21, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 4, 2012</study_first_posted>
  <last_update_submitted>June 9, 2015</last_update_submitted>
  <last_update_submitted_qc>June 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 10, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Nijmegen</investigator_affiliation>
    <investigator_full_name>Leo Heunks</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>levosimendan</keyword>
  <keyword>diaphragm function</keyword>
  <keyword>mechanically ventilated patients</keyword>
  <keyword>neuro-mechanical efficiency</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Weakness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Simendan</mesh_term>
  </intervention_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/NCT01721434
org study id: Levo2
nct id: NCT01721434
lead sponsor: 
collaborator: 
has dmc: No
Levosimendan is a relatively new drug that improves cardiac contractility in patients with
      heart failure. Its main mechanism of action is enhanced binding of calcium to the myocardial
      contractile proteins. Recent data from our lab showed that levosimendan improves
      contractility of human diaphragm in vitro (muscle fibers from COPD patient diaphragm) and in
      vivo (healthy subjects). Accordingly, levosimendan may appear of value in the treatment of
      disorders associated with impaired respiratory muscle function, such as mechanically
      ventilated patients.We hypothesize that levosimendan could improve respiratory muscle
      function in mechanically ventilated patients commencing a CPAP trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Neuro-mechanical efficiency of the diaphragm
time frame: Artefact-free periode in the last 10 minutes of each CPAP trial
description: The primary outcome measure is the neuro-mechanical efficiency(i.e. the ratio of diaphragm electrical activity and transdiaphragmatic pressure) of the diaphragm during a continuous positive airway pressure (CPAP) trial.
measure: Neuro-ventilatory efficiency of the diaphragm
time frame: Artefact-free periode in the last 10 minutes of each CPAP trial
description: A secondary outcome measure is the neuro-ventilatory efficiency (i.e. the ratio of diaphragm electrical activity and tidal volume) during a continuous positive airway pressure (CPAP) trial.
measure: Oxygen consumption (VO2)
time frame: Artefact-free periode in the last 10 minutes of each CPAP trial
description: A secondary outcome measure is the oxygen consumption during a continuous positive airway pressure (CPAP) trial.
measure: Partial pressure of oxygen in arterial blood (PaO2)
time frame: Last minute of the 30 minute CPAP trial
description: A secondary outcome measure is the PaO2 at the end of a continuous positive airway pressure (CPAP) trial.
measure: Accessory respiratory muscle activity
time frame: Measured during a one hour protocol after the second CPAP trial.
description: To determine the effects of levosimendan on accessory respiratory muscle function, ventilator settings are adapted after the last CPAP-trial.
measure: Carbon dioxide production (VCO2)
time frame: Artefact-free periode in the last 10 minutes of each CPAP trial
description: A secondary outcome measure is the carbon dioxide production during a continuous positive airway pressure (CPAP) trial.
measure: Partial pressure of carbon dioxide in arterial blood (PaCO2)
time frame: Last minute of the 30 minute CPAP trial
description: A secondary outcome measure is the PaCO2 at the and of a continuous positive airway pressure (CPAP) trial.
arm group label: Levosimendan
arm group type: Experimental
description: Levosimendan 0.2 ug/kg/min intravenous for a single 7 hours.
arm group label: Placebo
arm group type: Placebo Comparator
description: Similar coloured placebo intravenous for a single 7 hours
intervention type: Drug
intervention name: Levosimendan
arm group label: Levosimendan
other name: Simdax
intervention type: Drug
intervention name: Placebo
description: Similar coloured placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Leo Heunks, MD, PhD
role: Principal Investigator
affiliation: Radboud University Medical Center
last name: Leo MA Heunks, MD, PhD
phone: 024-3617273
email: l.heunks@ic.umcn.nl
last name: Jonne Doorduin, MSc
phone: 024-3617273
email: j.doorduin@ic.umcn.nl
facility: 
status: Recruiting
contact: 
contact backup: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Nijmegen
investigator full name: Leo Heunks
investigator title: MD, PhD
mesh term: Muscle Weakness
mesh term: Simendan