<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/NCT04476173</url>
  </required_header>
  <id_info>
    <org_study_id>ANEMON-SIRIO3</org_study_id>
    <nct_id>NCT04476173</nct_id>
  </id_info>
  <brief_title>ANalgesic Efficacy and Safety of MOrphiNe Versus Methoxyflurane in Patients With Acute Myocardial Infarction</brief_title>
  <acronym>ANEMON</acronym>
  <official_title>ANalgesic Efficacy and Safety of MOrphiNe Versus Methoxyflurane in Patients With Acute Myocardial Infarction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Collegium Medicum w Bydgoszczy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Collegium Medicum w Bydgoszczy</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate analgesic efficacy of inhaled methoxyflurane vs&#xD;
      intravenous morphine in patients presenting with acute ST-elevation (STEMI) / non&#xD;
      ST-elevation acute coronary syndrome (NSTE-ACS)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Platelet activation plays a pivotal role in the pathophysiology of acute coronary syndromes&#xD;
      (ACS). Pharmacological platelet inhibition with P2Y12 receptor antagonists and aspirin,&#xD;
      together with percutaneous coronary intervention (PCI) are the cornerstone of treatment of&#xD;
      ACS patients.&#xD;
&#xD;
      Chest pain and anxiety are both associated with sympathetic activation, which increases&#xD;
      workload of the heart. Relieving of these symptoms in acute myocardial infarction (AMI) is&#xD;
      expected to improve the balance between the demand for oxygen and its supply. Morphine, apart&#xD;
      from its analgesic effects, also alleviates the work of breathing and reduces anxiety.&#xD;
      However, despite its favourable analgesic and sedative actions, morphine also exerts adverse&#xD;
      effects, which include vomiting and reduction of gastrointestinal motility. These side&#xD;
      effects affect the intestinal absorption of oral drugs co-administered with morphine.&#xD;
      Previously performed randomized studies revealed unfavourable influence of morphine on the&#xD;
      pharmacokinetics of ticagrelor resulting in weaker and retarded antiplatelet effect.&#xD;
&#xD;
      Methoxyflurane was shown to be effective and well tolerated for the management of acute&#xD;
      traumatic pain with a rapid onset of analgesia. As it does not affect the μ-opioid receptors,&#xD;
      which inhibit propulsive motility and secretion of the gastro-intestinal tract,&#xD;
      methoxyflurane is not expected to decrease or delay absorption or effects of orally&#xD;
      administered drugs, including P2Y12 inhibitors, as well as to exert any other negative impact&#xD;
      in patients with ACS.&#xD;
&#xD;
      Before PCI for the index ACS, after obtaining informed consent patients will be enrolled and&#xD;
      randomly assigned with a secure on-line system in 1:1 ratio to one of two study arms.&#xD;
      Patients in the intervention arm will receive methoxyphlurane administered by inhalation,&#xD;
      whereas patients in the control arm will obtain morphine administered intravenously.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <phase>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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measure of pain intensity according to the Numeric Pain Rating Scale (NPRS) 2-3 minutes after drug administration in relation to pain intensity assessed before drug administration</measure>
    <time_frame>2-3 mins</time_frame>
    <description>NPRS score before and 2-3 minutes after drug administration in each study arm</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measure of pain intensity according to the Numeric Pain Rating Scale (NPRS) immediately after PCI in relation to pain intensity assessed before drug administration</measure>
    <time_frame>immediately after PCI</time_frame>
    <description>NPRS score before drug administration and and immediately after PCI in each study arm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse effects of evaluated therapies</measure>
    <time_frame>24 hours</time_frame>
    <description>nausea, vomiting, dry mouth, respiratory failure - need for intubation, headache, dizziness, drowsiness, loss of consciousness, death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for GPIIb/IIIa (glycoprotein IIb/IIIa) inhibitor administration during PCI due to large intracoronary thrombus</measure>
    <time_frame>24 hours</time_frame>
    <description>The percentage of patients who required GP IIb/IIIa administration in each study arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Angiographic effect of PCI using Thrombolysis In Myocardial Infarction (TIMI) scale</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>central analysis of coronary angiography after PCI according to Thrombolysis In Myocardial Infarction (TIMI) scale (TIMI 0 to TIMI 3; where TIMI 0 corresponds with no antegrade flow beyond the point of occlusion whereas TIMI 3 - normal flow with complete filling of the distal territory)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Angiographic effect of PCI using TIMI Myocardial Perfusion Grade (TMPG) scale</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>central analysis of coronary angiography after PCI according to TIMI Myocardial Perfusion Grade (TMPG) scale (TMPG 0 to TMPG 3, where TMPG 0 corresponds with failure of dye to enter the microvasculature, indicating a lack of tissue level perfusion whereas TMPG 3 - normal entry and exit of dye from the microvasculature)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ST elevation resolution in STEMI patients after PCI</measure>
    <time_frame>1 hour after PCI</time_frame>
    <description>central analysis of ST elevation reduction in STEMI patients with a 70% resolution cut-off</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>ST Elevation Myocardial Infarction</condition>
  <condition>Non ST Segment Elevation Acute Coronary Syndrome</condition>
  <arm_group>
    <arm_group_label>Methoxyflurane</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with inhaled methoxyflurane (3 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Morphine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients treated with intravenous morphine (5 mg)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methoxyflurane - Penthrox</intervention_name>
    <description>ACS patients who received inhaled methoxyflurane as analgesic treatment</description>
    <arm_group_label>Methoxyflurane</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>ACS patients who received intravenous morphine as analgesic treatment</description>
    <arm_group_label>Morphine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation acute&#xD;
             coronary syndrome (NSTE-ACS)&#xD;
&#xD;
          -  patients aged from 18 to 80 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  manifest infection or inflammatory state&#xD;
&#xD;
          -  cardiogenic shock during screening for eligibility&#xD;
&#xD;
          -  respiratory failure&#xD;
&#xD;
          -  heart failure (NYHA class III or IV during screening for eligibility)&#xD;
&#xD;
          -  uncontrolled hypertension (systolic blood pressure &gt;180 mmHg or diastolic blood&#xD;
             pressure &gt;100 mmHg)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jacek Kubica, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Collegium Medicum w Bydgoszczy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Agata Kosobucka, PhD</last_name>
    <phone>+48 525854023</phone>
    <email>akosobucka@wp.pl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Piotr Niezgoda, MD</last_name>
    <phone>+48 525854023</phone>
    <email>piotr.niezgoda1986@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Cardiology</name>
      <address>
        <city>Bydgoszcz</city>
        <state>Kujawsko-Pomorskie</state>
        <zip>85-094</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Agata Kosobucka, PhD</last_name>
      <phone>+48 525854023</phone>
      <email>akosobucka@wp.pl</email>
    </contact>
    <investigator>
      <last_name>Jacek Kubica, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Collegium Medicum w Bydgoszczy</investigator_affiliation>
    <investigator_full_name>Jacek Kubica</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Acute Coronary Syndrome</mesh_term>
    <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Methoxyflurane</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04476173
org study id: ANEMON-SIRIO3
nct id: NCT04476173
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate analgesic efficacy of inhaled methoxyflurane vs
      intravenous morphine in patients presenting with acute ST-elevation (STEMI) / non
      ST-elevation acute coronary syndrome (NSTE-ACS)
Platelet activation plays a pivotal role in the pathophysiology of acute coronary syndromes
      (ACS). Pharmacological platelet inhibition with P2Y12 receptor antagonists and aspirin,
      together with percutaneous coronary intervention (PCI) are the cornerstone of treatment of
      ACS patients.

      Chest pain and anxiety are both associated with sympathetic activation, which increases
      workload of the heart. Relieving of these symptoms in acute myocardial infarction (AMI) is
      expected to improve the balance between the demand for oxygen and its supply. Morphine, apart
      from its analgesic effects, also alleviates the work of breathing and reduces anxiety.
      However, despite its favourable analgesic and sedative actions, morphine also exerts adverse
      effects, which include vomiting and reduction of gastrointestinal motility. These side
      effects affect the intestinal absorption of oral drugs co-administered with morphine.
      Previously performed randomized studies revealed unfavourable influence of morphine on the
      pharmacokinetics of ticagrelor resulting in weaker and retarded antiplatelet effect.

      Methoxyflurane was shown to be effective and well tolerated for the management of acute
      traumatic pain with a rapid onset of analgesia. As it does not affect the μ-opioid receptors,
      which inhibit propulsive motility and secretion of the gastro-intestinal tract,
      methoxyflurane is not expected to decrease or delay absorption or effects of orally
      administered drugs, including P2Y12 inhibitors, as well as to exert any other negative impact
      in patients with ACS.

      Before PCI for the index ACS, after obtaining informed consent patients will be enrolled and
      randomly assigned with a secure on-line system in 1:1 ratio to one of two study arms.
      Patients in the intervention arm will receive methoxyphlurane administered by inhalation,
      whereas patients in the control arm will obtain morphine administered intravenously.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Measure of pain intensity according to the Numeric Pain Rating Scale (NPRS) 2-3 minutes after drug administration in relation to pain intensity assessed before drug administration
time frame: 2-3 mins
description: NPRS score before and 2-3 minutes after drug administration in each study arm
measure: Measure of pain intensity according to the Numeric Pain Rating Scale (NPRS) immediately after PCI in relation to pain intensity assessed before drug administration
time frame: immediately after PCI
description: NPRS score before drug administration and and immediately after PCI in each study arm
measure: Adverse effects of evaluated therapies
time frame: 24 hours
description: nausea, vomiting, dry mouth, respiratory failure - need for intubation, headache, dizziness, drowsiness, loss of consciousness, death
measure: Need for GPIIb/IIIa (glycoprotein IIb/IIIa) inhibitor administration during PCI due to large intracoronary thrombus
time frame: 24 hours
description: The percentage of patients who required GP IIb/IIIa administration in each study arm
measure: Angiographic effect of PCI using Thrombolysis In Myocardial Infarction (TIMI) scale
time frame: through study completion, an average of 1 year
description: central analysis of coronary angiography after PCI according to Thrombolysis In Myocardial Infarction (TIMI) scale (TIMI 0 to TIMI 3; where TIMI 0 corresponds with no antegrade flow beyond the point of occlusion whereas TIMI 3 - normal flow with complete filling of the distal territory)
measure: Angiographic effect of PCI using TIMI Myocardial Perfusion Grade (TMPG) scale
time frame: through study completion, an average of 1 year
description: central analysis of coronary angiography after PCI according to TIMI Myocardial Perfusion Grade (TMPG) scale (TMPG 0 to TMPG 3, where TMPG 0 corresponds with failure of dye to enter the microvasculature, indicating a lack of tissue level perfusion whereas TMPG 3 - normal entry and exit of dye from the microvasculature)
measure: ST elevation resolution in STEMI patients after PCI
time frame: 1 hour after PCI
description: central analysis of ST elevation reduction in STEMI patients with a 70% resolution cut-off
arm group label: Methoxyflurane
arm group type: Experimental
description: Patients treated with inhaled methoxyflurane (3 mg)
arm group label: Morphine
arm group type: Active Comparator
description: Patients treated with intravenous morphine (5 mg)
intervention type: Drug
intervention name: Methoxyflurane - Penthrox
description: ACS patients who received inhaled methoxyflurane as analgesic treatment
arm group label: Methoxyflurane
intervention type: Drug
intervention name: Morphine
description: ACS patients who received intravenous morphine as analgesic treatment
arm group label: Morphine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Jacek Kubica, Professor
role: Principal Investigator
affiliation: Collegium Medicum w Bydgoszczy
last name: Agata Kosobucka, PhD
phone: +48 525854023
email: akosobucka@wp.pl
last name: Piotr Niezgoda, MD
phone: +48 525854023
email: piotr.niezgoda1986@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Poland
responsible party type: Principal Investigator
investigator affiliation: Collegium Medicum w Bydgoszczy
investigator full name: Jacek Kubica
investigator title: Professor
mesh term: Myocardial Infarction
mesh term: Acute Coronary Syndrome
mesh term: ST Elevation Myocardial Infarction
mesh term: Infarction
mesh term: Morphine
mesh term: Methoxyflurane
sharing ipd: No