<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/NCT03237910</url>
  </required_header>
  <id_info>
    <org_study_id>IRFMN-7167-7429</org_study_id>
    <nct_id>NCT03237910</nct_id>
  </id_info>
  <brief_title>Real Time Amplitude Spectrum Area to Guide Defibrillation</brief_title>
  <acronym>AMSA</acronym>
  <official_title>AMplitude Spectrum Area to Guide Defibrillation During Cardiopulmonary Resuscitation in Out-of-hospital Cardiac Arrest Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mario Negri Institute for Pharmacological Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Commission</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zoll Medical Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mario Negri Institute for Pharmacological Research</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_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      AMSA trial is a multicenter, randomized, controlled study in out-of-hospital cardiac arrest&#xD;
      patients.&#xD;
&#xD;
      The purpose of the study is to test the hypothesis that a real time AMSA analysis during CPR&#xD;
      may predict the success of defibrillation and optimize the timing of defibrillation delivery.&#xD;
&#xD;
      The primary end-point is the efficacy of the AMSA-CPR: termination of VF/VT with achievement&#xD;
      of ROSC for an AMSA ≥ 15.5 mV-Hz&#xD;
&#xD;
      All patients meeting inclusion/exclusion criteria and receiving cardiopulmonary resuscitation&#xD;
      are randomized into two groups: AMSA-guided CPR or standard CPR.&#xD;
&#xD;
      In the AMSA-CPR group, AMSA value suggests when the rescuer should deliver the defibrillation&#xD;
      attempt; In the Standard-CPR group, the defibrillation is delivered based on the 2015&#xD;
      European Resuscitation Council (ERC) CPR guidelines.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the AMSA-CPR intervention, upon arrival of the advanced life support (ALS) rescue team at&#xD;
      the cardiac arrest scene and application of the defibrillatory pads to the patient's chest&#xD;
      and power on of the defibrillator with the real time AMSA analysis:&#xD;
&#xD;
        -  If AMSA is ≥ 15.5 mV-Hz, an immediate defibrillation is attempted, followed by CPR&#xD;
&#xD;
        -  If AMSA is &lt; 15.5 mV-Hz, defibrillation is not attempted and CPR is delivered&#xD;
&#xD;
        -  During the 2-min cycle of CPR, AMSA is measured during pauses for ventilations (every 30&#xD;
           CC, approximately every 20/25 sec). If an AMSA value ≥ 15.5 mV-Hz is achieved prior to&#xD;
           cycle completion, an immediate defibrillation is delivered (thus the defibrillation&#xD;
           attempt is anticipated)&#xD;
&#xD;
      After completion of the first 2-min CPR cycle:&#xD;
&#xD;
        -  If AMSA is ≤ 6.5 mV-Hz, the defibrillation is not attempted but CPR is continued&#xD;
&#xD;
        -  If AMSA is &gt; 6.5 mV-Hz, an immediate defibrillation attempt is delivered, followed by&#xD;
           CPR&#xD;
&#xD;
        -  During the 2-min cycle of CPR, AMSA is measured during pauses for ventilations (every 30&#xD;
           CC, approximately every 20/25 sec). If an AMSA value ≥ 15.5 mV-Hz is achieved prior to&#xD;
           cycle completion, an immediate defibrillation is delivered&#xD;
&#xD;
      After completion of the second 2-min CPR cycle and till the end of the resuscitative&#xD;
      intervention:&#xD;
&#xD;
      • CPR is continued based on standard 2015 ERC guidelines (a defibrillation attempt every&#xD;
      2-min CPR cycles), except for the possibility to anticipate the defibrillation attempt if&#xD;
      AMSA becomes ≥ 15.5 mV-Hz during the CPR cycle.&#xD;
&#xD;
      In the standard CPR intervention, upon arrival of the ALS team at the cardiac arrest scene,&#xD;
      and application of the defibrillatory pads to the patient's chest and power on of the&#xD;
      defibrillator:&#xD;
&#xD;
      • a defibrillation is immediately attempted and CPR is then started and continued for 2- min.&#xD;
      Analysis of rhythm and subsequent defibrillation attempts are performed every 2-min CPR&#xD;
      cycles.&#xD;
&#xD;
      In both study groups, the quality of CC and ventilation is monitored in real time thought the&#xD;
      feedback integrated into the defibrillator.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    low rate recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">April 28, 2019</start_date>
  <completion_date type="Actual">July 26, 2021</completion_date>
  <primary_completion_date type="Actual">July 26, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Return of spontaneous circulation (ROSC)</measure>
    <time_frame>At day 0: from date of initiation of the cardiopulmonary resuscitation (CPR) maneuvres up to ROSC or up to 1 hour of CPR (which comes first)</time_frame>
    <description>Termination of ventricular fibrillation with achievement of ROSC for an AMSA value ≥ 15.5 mV-Hz</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Defibrillation attempts</measure>
    <time_frame>At day 0: from date of initiation of the cardiopulmonary resuscitation (CPR) maneuvres up to ROSC or up to 1 hour of CPR (which comes first)</time_frame>
    <description>Number of defibrillations to achieve ROSC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CPR duration</measure>
    <time_frame>At day 0: from date of initiation of the cardiopulmonary resuscitation (CPR) maneuvres up to ROSC or up to 1 hour of CPR (which comes first)</time_frame>
    <description>duration of CPR in minutes prior to achieve ROSC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac troponins</measure>
    <time_frame>at 6 and 24 hours after ICU admission</time_frame>
    <description>assessment of circulating levels of high sensitive cardiac troponin T in plasma as marker of cardiac injury</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short term survival</measure>
    <time_frame>at hospital admission and 24 hours after ROSC</time_frame>
    <description>number of patients alive after initial resuscitation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long term survival</measure>
    <time_frame>at 1 and 6 months after ROSC</time_frame>
    <description>number of patients alive after initial resuscitation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Out-Of-Hospital Cardiac Arrest</condition>
  <condition>Ventricular Fibrillation</condition>
  <arm_group>
    <arm_group_label>AMSA-CPR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The professional rescuer decides to deliver the defibrillation attempt based on the AMSA value displayed in the defibrillator</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard-CPR</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The defibrillation is delivered based on the 2015 European Resuscitation Council CPR guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>AMSA</intervention_name>
    <description>A non-invasive and real time VF (Amplitude Spectrum Area) AMSA analysis is performed during chest compression pauses for delivery of 2 ventilations, from the ECG acquired from the conventional defibrillatory pads</description>
    <arm_group_label>AMSA-CPR</arm_group_label>
    <other_name>VF waveform analysis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Defibrillation</intervention_name>
    <description>delivery of the defibrillation is attempted to terminate VF either based on AMSA value (in the AMSA-CPR arm) or every 2-min CPR cycle as recommended by current guidelines (in the Standard-CPR arm)</description>
    <arm_group_label>AMSA-CPR</arm_group_label>
    <arm_group_label>Standard-CPR</arm_group_label>
    <other_name>electric countershock</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>CPR</intervention_name>
    <description>chest compressions and ventilations at a rate of 30:2</description>
    <arm_group_label>AMSA-CPR</arm_group_label>
    <arm_group_label>Standard-CPR</arm_group_label>
    <other_name>resuscitation maneuvres</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All adult patients (age ≥ 18) suffering of out-of-hospital non traumatic cardiac arrest of&#xD;
        presumably cardiac etiology with a presenting shockable rhythm requiring electrical&#xD;
        defibrillation: Ventricular Fibrillation and pulseless Ventricular Tachycardia.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt; 18 years old&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  cardiac arrest with a non-shockable rhythm (pulseless electrical activity and&#xD;
             asystole)&#xD;
&#xD;
          -  a defibrillation delivered by an AED prior to ALS arrival&#xD;
&#xD;
          -  cardiac arrest of traumatic origin&#xD;
&#xD;
          -  non-cardiac cause of cardiac arrest&#xD;
&#xD;
          -  presumable irreversible death or known terminal illness at the beginning of ALS&#xD;
&#xD;
          -  clinical death&#xD;
&#xD;
          -  participation in another clinical or device trial within the previous 30 days&#xD;
&#xD;
          -  refused informed consent to the use of data.&#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>Giuseppe Ristagno, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Istituto Di Ricerche Farmacologiche Mario Negri</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Roberto Latini, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Istituto Di Ricerche Farmacologiche Mario Negri</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UOC Rianimazione-Emergenza Territoriale 118, Dipartimento di Emergenza, Ospedale Maggiore - AUSL di Bologna</name>
      <address>
        <city>Bologna</city>
        <zip>40124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SOREU Metropolitana - AREU ASST, Grande Ospedale Metropolitano Niguarda</name>
      <address>
        <city>Milano</city>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <link>
    <url>http://cordis.europa.eu/project/rcn/207233_en.html</url>
    <description>EU Framework Horizon 2020 Programme under grant agreement no. 733381: European Sudden Cardiac Arrest network: towards Prevention, Education and New Treatment (ESCAPE-NET)</description>
  </link>
  <link>
    <url>https://www.erc.edu/projects/escape-net</url>
    <description>ESCAPE NET in ERC website</description>
  </link>
  <link>
    <url>https://www.escardio.org/Sub-specialty-communities/European-Heart-Rhythm-Association-(EHRA)/Research/escape-net</url>
    <description>ESCAPE NET in EHRA website</description>
  </link>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>September 30, 2022</last_update_submitted>
  <last_update_submitted_qc>September 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>amplitude spectrum area</keyword>
  <keyword>defibrillation</keyword>
  <keyword>waveform analysis</keyword>
  <keyword>cardiopulmonary resuscitation</keyword>
  <keyword>cardiac arrest</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Arrest</mesh_term>
    <mesh_term>Out-of-Hospital Cardiac Arrest</mesh_term>
    <mesh_term>Ventricular Fibrillation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03237910
org study id: IRFMN-7167-7429
nct id: NCT03237910
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
AMSA trial is a multicenter, randomized, controlled study in out-of-hospital cardiac arrest
      patients.

      The purpose of the study is to test the hypothesis that a real time AMSA analysis during CPR
      may predict the success of defibrillation and optimize the timing of defibrillation delivery.

      The primary end-point is the efficacy of the AMSA-CPR: termination of VF/VT with achievement
      of ROSC for an AMSA ≥ 15.5 mV-Hz

      All patients meeting inclusion/exclusion criteria and receiving cardiopulmonary resuscitation
      are randomized into two groups: AMSA-guided CPR or standard CPR.

      In the AMSA-CPR group, AMSA value suggests when the rescuer should deliver the defibrillation
      attempt; In the Standard-CPR group, the defibrillation is delivered based on the 2015
      European Resuscitation Council (ERC) CPR guidelines.
In the AMSA-CPR intervention, upon arrival of the advanced life support (ALS) rescue team at
      the cardiac arrest scene and application of the defibrillatory pads to the patient's chest
      and power on of the defibrillator with the real time AMSA analysis:

        -  If AMSA is ≥ 15.5 mV-Hz, an immediate defibrillation is attempted, followed by CPR

        -  If AMSA is < 15.5 mV-Hz, defibrillation is not attempted and CPR is delivered

        -  During the 2-min cycle of CPR, AMSA is measured during pauses for ventilations (every 30
           CC, approximately every 20/25 sec). If an AMSA value ≥ 15.5 mV-Hz is achieved prior to
           cycle completion, an immediate defibrillation is delivered (thus the defibrillation
           attempt is anticipated)

      After completion of the first 2-min CPR cycle:

        -  If AMSA is ≤ 6.5 mV-Hz, the defibrillation is not attempted but CPR is continued

        -  If AMSA is > 6.5 mV-Hz, an immediate defibrillation attempt is delivered, followed by
           CPR

        -  During the 2-min cycle of CPR, AMSA is measured during pauses for ventilations (every 30
           CC, approximately every 20/25 sec). If an AMSA value ≥ 15.5 mV-Hz is achieved prior to
           cycle completion, an immediate defibrillation is delivered

      After completion of the second 2-min CPR cycle and till the end of the resuscitative
      intervention:

      • CPR is continued based on standard 2015 ERC guidelines (a defibrillation attempt every
      2-min CPR cycles), except for the possibility to anticipate the defibrillation attempt if
      AMSA becomes ≥ 15.5 mV-Hz during the CPR cycle.

      In the standard CPR intervention, upon arrival of the ALS team at the cardiac arrest scene,
      and application of the defibrillatory pads to the patient's chest and power on of the
      defibrillator:

      • a defibrillation is immediately attempted and CPR is then started and continued for 2- min.
      Analysis of rhythm and subsequent defibrillation attempts are performed every 2-min CPR
      cycles.

      In both study groups, the quality of CC and ventilation is monitored in real time thought the
      feedback integrated into the defibrillator.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Return of spontaneous circulation (ROSC)
time frame: At day 0: from date of initiation of the cardiopulmonary resuscitation (CPR) maneuvres up to ROSC or up to 1 hour of CPR (which comes first)
description: Termination of ventricular fibrillation with achievement of ROSC for an AMSA value ≥ 15.5 mV-Hz
measure: Defibrillation attempts
time frame: At day 0: from date of initiation of the cardiopulmonary resuscitation (CPR) maneuvres up to ROSC or up to 1 hour of CPR (which comes first)
description: Number of defibrillations to achieve ROSC
measure: CPR duration
time frame: At day 0: from date of initiation of the cardiopulmonary resuscitation (CPR) maneuvres up to ROSC or up to 1 hour of CPR (which comes first)
description: duration of CPR in minutes prior to achieve ROSC
measure: Cardiac troponins
time frame: at 6 and 24 hours after ICU admission
description: assessment of circulating levels of high sensitive cardiac troponin T in plasma as marker of cardiac injury
measure: Short term survival
time frame: at hospital admission and 24 hours after ROSC
description: number of patients alive after initial resuscitation
measure: Long term survival
time frame: at 1 and 6 months after ROSC
description: number of patients alive after initial resuscitation
arm group label: AMSA-CPR
arm group type: Experimental
description: The professional rescuer decides to deliver the defibrillation attempt based on the AMSA value displayed in the defibrillator
arm group label: Standard-CPR
arm group type: Active Comparator
description: The defibrillation is delivered based on the 2015 European Resuscitation Council CPR guidelines
intervention type: Diagnostic Test
intervention name: AMSA
description: A non-invasive and real time VF (Amplitude Spectrum Area) AMSA analysis is performed during chest compression pauses for delivery of 2 ventilations, from the ECG acquired from the conventional defibrillatory pads
arm group label: AMSA-CPR
other name: VF waveform analysis
intervention type: Procedure
intervention name: Defibrillation
description: delivery of the defibrillation is attempted to terminate VF either based on AMSA value (in the AMSA-CPR arm) or every 2-min CPR cycle as recommended by current guidelines (in the Standard-CPR arm)
arm group label: AMSA-CPR
arm group label: Standard-CPR
other name: electric countershock
intervention type: Procedure
intervention name: CPR
description: chest compressions and ventilations at a rate of 30:2
arm group label: AMSA-CPR
arm group label: Standard-CPR
other name: resuscitation maneuvres
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Giuseppe Ristagno, MD, PhD
role: Study Chair
affiliation: Istituto Di Ricerche Farmacologiche Mario Negri
last name: Roberto Latini, MD
role: Study Chair
affiliation: Istituto Di Ricerche Farmacologiche Mario Negri
facility: 
facility: 
country: Italy
url: http://cordis.europa.eu/project/rcn/207233_en.html
description: EU Framework Horizon 2020 Programme under grant agreement no. 733381: European Sudden Cardiac Arrest network: towards Prevention, Education and New Treatment (ESCAPE-NET)
url: https://www.erc.edu/projects/escape-net
description: ESCAPE NET in ERC website
url: https://www.escardio.org/Sub-specialty-communities/European-Heart-Rhythm-Association-(EHRA)/Research/escape-net
description: ESCAPE NET in EHRA website
responsible party type: Sponsor
mesh term: Heart Arrest
mesh term: Out-of-Hospital Cardiac Arrest
mesh term: Ventricular Fibrillation
sharing ipd: Undecided