<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/NCT04420455</url>
  </required_header>
  <id_info>
    <org_study_id>2019-1432</org_study_id>
    <nct_id>NCT04420455</nct_id>
  </id_info>
  <brief_title>The Effects of Enoximone in Acute Exacerbation COPD</brief_title>
  <official_title>The Effects of Enoximone in Acute Exacerbation COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rijnstate Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rijnstate Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Introduction:&#xD;
&#xD;
      The pharmacodynamic properties of enoximone could be beneficial for patients with an Acute&#xD;
      Exacerbation COPD (AE-COPD). This research will focus on patients suffering of a severe&#xD;
      AE-COPD and the bronchodilatory and inotropic effects of lower doses of enoximone. The main&#xD;
      objective of the pilot study is to investigate if there is a bronchodilatory effect of&#xD;
      enoximone in patients with AE-COPD. Secondary objective is to investigate a dose&#xD;
      responsiveness in a range between 0.5 and 1.5 mg/kg enoximone.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      The study design is a prospective interventional non-randomized clinical series study&#xD;
      involving patients admitted and intubated at the Intensive Care Unit (ICU) with an AE-COPD.&#xD;
      Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval. The&#xD;
      primary objective is a reduction in auto-positive end-expiratory pressure (PEEP) after&#xD;
      enoximone compared to baseline. A dose-titration will test for dose dependency. Secondary&#xD;
      objectives are a reduction in ventilator pressures, a reduction in pulmonary artery pressures&#xD;
      and an increase in cardiac output.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ventilator will be set during the study period at Volume Controle, 6 ml/kg, 5 PEEP and a&#xD;
      respiratory rate of 15 bpm with an I:E-ratio of 1:2.&#xD;
&#xD;
      Salbutamol/ipratropium bromide and magnesium sulphate will be administered at baseline (t=0h)&#xD;
      and measurements will be made for an hour.&#xD;
&#xD;
      At T=1h the first dose of 0.5 mg/kg enoximone will be administered and will be repeated at&#xD;
      T=2h and T=3h. Ventilator derived variables will be obtained every fifteen minutes and&#xD;
      echocardiography, arterial and central venous bloodgas analyses every hour until t=6h.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    A limited number of inclusions due to the Covid-pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">May 12, 2020</start_date>
  <completion_date type="Actual">December 21, 2021</completion_date>
  <primary_completion_date type="Actual">December 21, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PEEP</measure>
    <time_frame>within 6 hoursmeasured every 15 minutes</time_frame>
    <description>Reduction in intrinsic PEEP, in cmH2O</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lung compliance</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>ml/H2O</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Airway resistence</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>cmH2O/L/sec</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VEI</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VCO2</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>ml/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>etCO2</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>kPa</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vd/Vt</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>Measured by Bohr-equation, in percentage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FiO2</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>percentage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Shunt fraction</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>measured by Fick-equation, using the SvO2, in percentage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac Output</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>Measured by echocardiography (LVOT VTI), ml/hr</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RVSP</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>Measured by echocardiography, in mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TAPSE</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>Measured by echocardiography, in mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MAPSE</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>Measured by echocardiography, in mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LV Ejection Fraction</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>Measured by echocardiography, in percentage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bloodgas analysis</measure>
    <time_frame>within 6 hours, measured every hour</time_frame>
    <description>Arterial bloodgas analysis and central venous gas analysis (through catheter placed in superior vena cava)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>COPD Exacerbation</condition>
  <condition>Enoximone</condition>
  <condition>Phosphodiesterase Inhibitor</condition>
  <arm_group>
    <arm_group_label>Enoximone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoximone</intervention_name>
    <description>Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.</description>
    <arm_group_label>Enoximone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with an AE-COPD for which intubation occurred within 24 hours before&#xD;
             enrolment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with known asthma or interstitial lung disease (ILD)&#xD;
&#xD;
          -  Known neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple&#xD;
             Sclerosis (MS), Guillain-Barre and Dementia&#xD;
&#xD;
          -  Hypertrophic obstructive cardiomyopathy (HOCM)&#xD;
&#xD;
          -  Severe aortic stenosis with aortic valve area &lt; 1cm2&#xD;
&#xD;
          -  Known ventricular arrhythmias&#xD;
&#xD;
          -  Severe kidney disorders with Glomerular Filtration Rate (GFR) &lt; 30&#xD;
&#xD;
          -  Severe liver insufficiency with spontaneous PT/INR &gt; 1.5&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Lactation&#xD;
&#xD;
          -  High dose-diuretics use (daily dose of &gt;480 mg furosemide)&#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>M.V. Koning</name>
      <address>
        <city>Arnhem</city>
        <state>M</state>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 31, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>December 23, 2021</last_update_submitted>
  <last_update_submitted_qc>December 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoximone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>after publication</ipd_time_frame>
    <ipd_access_criteria>upon reasonable request, available by the researchers</ipd_access_criteria>
  </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/NCT04420455
org study id: 2019-1432
nct id: NCT04420455
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Introduction:

      The pharmacodynamic properties of enoximone could be beneficial for patients with an Acute
      Exacerbation COPD (AE-COPD). This research will focus on patients suffering of a severe
      AE-COPD and the bronchodilatory and inotropic effects of lower doses of enoximone. The main
      objective of the pilot study is to investigate if there is a bronchodilatory effect of
      enoximone in patients with AE-COPD. Secondary objective is to investigate a dose
      responsiveness in a range between 0.5 and 1.5 mg/kg enoximone.

      Methods:

      The study design is a prospective interventional non-randomized clinical series study
      involving patients admitted and intubated at the Intensive Care Unit (ICU) with an AE-COPD.
      Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval. The
      primary objective is a reduction in auto-positive end-expiratory pressure (PEEP) after
      enoximone compared to baseline. A dose-titration will test for dose dependency. Secondary
      objectives are a reduction in ventilator pressures, a reduction in pulmonary artery pressures
      and an increase in cardiac output.
Ventilator will be set during the study period at Volume Controle, 6 ml/kg, 5 PEEP and a
      respiratory rate of 15 bpm with an I:E-ratio of 1:2.

      Salbutamol/ipratropium bromide and magnesium sulphate will be administered at baseline (t=0h)
      and measurements will be made for an hour.

      At T=1h the first dose of 0.5 mg/kg enoximone will be administered and will be repeated at
      T=2h and T=3h. Ventilator derived variables will be obtained every fifteen minutes and
      echocardiography, arterial and central venous bloodgas analyses every hour until t=6h.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PEEP
time frame: within 6 hoursmeasured every 15 minutes
description: Reduction in intrinsic PEEP, in cmH2O
measure: Lung compliance
time frame: within 6 hours, measured every hour
description: ml/H2O
measure: Airway resistence
time frame: within 6 hours, measured every hour
description: cmH2O/L/sec
measure: VEI
time frame: within 6 hours, measured every hour
description: ml
measure: VCO2
time frame: within 6 hours, measured every hour
description: ml/min
measure: etCO2
time frame: within 6 hours, measured every hour
description: kPa
measure: Vd/Vt
time frame: within 6 hours, measured every hour
description: Measured by Bohr-equation, in percentage
measure: FiO2
time frame: within 6 hours, measured every hour
description: percentage
measure: Shunt fraction
time frame: within 6 hours, measured every hour
description: measured by Fick-equation, using the SvO2, in percentage
measure: Cardiac Output
time frame: within 6 hours, measured every hour
description: Measured by echocardiography (LVOT VTI), ml/hr
measure: RVSP
time frame: within 6 hours, measured every hour
description: Measured by echocardiography, in mmHg
measure: TAPSE
time frame: within 6 hours, measured every hour
description: Measured by echocardiography, in mm
measure: MAPSE
time frame: within 6 hours, measured every hour
description: Measured by echocardiography, in mm
measure: LV Ejection Fraction
time frame: within 6 hours, measured every hour
description: Measured by echocardiography, in percentage
measure: Bloodgas analysis
time frame: within 6 hours, measured every hour
description: Arterial bloodgas analysis and central venous gas analysis (through catheter placed in superior vena cava)
arm group label: Enoximone
arm group type: Experimental
description: Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.
intervention type: Drug
intervention name: Enoximone
description: Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.
arm group label: Enoximone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Enoximone
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: after publication
ipd access criteria: upon reasonable request, available by the researchers