<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/NCT02225561</url>
  </required_header>
  <id_info>
    <org_study_id>P130946</org_study_id>
    <secondary_id>2014-002010-24</secondary_id>
    <nct_id>NCT02225561</nct_id>
  </id_info>
  <brief_title>SNPeCPR In Cardiac Arrest REsuscitation</brief_title>
  <acronym>SICARE</acronym>
  <official_title>SNPeCPR Pour la prIse en Charge Des Arrêts CaRdiaques Extrahospitaliers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Approximately 50,000 patients are victims of out of hospital cardiac arrest every year in&#xD;
      France. Despite cardiopulmonary resuscitation (CPR) and many studies on the topic&#xD;
      resuscitation survival after cardiac arrest remains low (1-8%) and has not changed&#xD;
      significantly over the past five decades.It has recently been shown that the combination of&#xD;
      different non-invasive therapies, cardiopulmonary resuscitation with mechanical CPR with&#xD;
      automated compression / decompression and an impedance threshold device, can increase the&#xD;
      rate of return of spontaneous circulation and short and long term survival after cardiac&#xD;
      arrest.We propose to study a new cardiopulmonary resuscitation called SNPeCPR (Sodium&#xD;
      nitroprusside enhanced cardiopulmonary resuscitation), which includes two components:a) a&#xD;
      mechanical component: cardiopulmonary resuscitation with automated mechanical external chest&#xD;
      compression and an impedance threshold deviceb) a pharmacological component: sodium&#xD;
      nitroprusside, an effective arterial vasodilator that decrease vascular resistance, and&#xD;
      improve flow in vital organs.Our hypothesis is that SNPeCPR should improve the return of&#xD;
      spontaneous circulation rate during cardiac arrest.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. OBJECTIVES The objective of this study is to demonstrate the superiority of Sodium&#xD;
           nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) on optimized standard&#xD;
           cardiopulmonary resuscitation.&#xD;
&#xD;
           SNPeCPR includes two components:&#xD;
&#xD;
             1. a mechanical component: cardiopulmonary resuscitation with automated mechanical&#xD;
                external chest compression and an impedance threshold device&#xD;
&#xD;
             2. a pharmacological component: sodium nitroprusside, an effective arterial&#xD;
                vasodilator that decreasing vascular resistance, facilitates flow elevation in&#xD;
                vital organs.&#xD;
&#xD;
           1.1. Main Objective : Assess the interests of the administration of sodium nitroprusside&#xD;
           during enhanced cardiopulmonary resuscitation.&#xD;
&#xD;
           1.2. Secondary Objectives : To evaluate the effect of sodium nitroprusside on various&#xD;
           parameters before and after the return of spontaneous circulation.&#xD;
&#xD;
           1.3. Outcome Measures : In this declaration, all the criterions measures before ROSC&#xD;
           have been note as t=0 minute.&#xD;
&#xD;
           For the elements were the timeframe is a variable, ICU and hospital discharge, they have&#xD;
           been declare at 1 and 2 weeks respectively.&#xD;
&#xD;
        2. NAME AND DESCRIPTION OF THE INVESTIGATIONAL DRUG Sodium nitroprusside (SNP) is a potent&#xD;
           vasodilator that we will use in cardiac arrest to optimize vital organs perfusion. The&#xD;
           purpose of CPR is to provide oxygenated blood to vital organs that are most susceptible&#xD;
           to ischemic insult (brain and heart). Since the mechanical combination (cardiopulmonary&#xD;
           resuscitation with automated mechanical external chest compression and an impedance&#xD;
           threshold device) provides excellent perfusion pressure, the flow should be optimized&#xD;
           pharmacological with vasodilation. The SNP reduces arterial vasoconstriction and&#xD;
           enhances microcirculation. Furthermore, SNP significantly reduces vascular resistance&#xD;
           and decreases cardiac ejection afterload. Therefore, SNPeCPR can significantly increase&#xD;
           the flow of blood and optimize carotid and coronary flow.&#xD;
&#xD;
        3. PROCEDURE During cardiac arrest resuscitation, patients will be included in the study&#xD;
           after the investigator has verified the inclusion and non-inclusion criterion. A sealed&#xD;
           box containing SNP or the placebo will then be open in the increasing numbers of&#xD;
           randomization list.&#xD;
&#xD;
           Whatever the allocated treatment (nitroprusside or Placebo [5% glucose solution]),&#xD;
           cardiopulmonary resuscitation protocol will be realize as recommended by the 2010&#xD;
           European Resuscitation Council and described as follows:&#xD;
&#xD;
             -  cardiopulmonary resuscitation will be performed continuously without posing for&#xD;
                control pulse until the first defibrillation attempt. As soon as possible manual&#xD;
                CPR will be replace by automated mechanical external chest compression (LUCAS® -&#xD;
                Lund University Cardiopulmonary Assist System) and an impedance threshold device&#xD;
                (ResQPOD®).&#xD;
&#xD;
             -  placement of a peripheral intravenous (IV) or intraosseous (IO) line. This&#xD;
                placement will be privileged to intubation,&#xD;
&#xD;
             -  when the peripheral intravenous or intraosseous line is set, 1.96 mg sodium&#xD;
                nitroprusside (SNP) / placebo will be injected, followed by injection of 10 ml&#xD;
                saline for intravenous flush (t = 0 minutes).&#xD;
&#xD;
             -  1 mg of epinephrine will be injected at t = 2 minutes,&#xD;
&#xD;
             -  an external electric shock (EEC) will be realized at t = 3 minutes when the&#xD;
                electric heart type allows it (ventricular fibrillation or ventricular&#xD;
                tachycardia),&#xD;
&#xD;
             -  0.98 mg sodium nitroprusside / placebo will be injected at t = 4 minutes, followed&#xD;
                by an injection of 10 ml of saline for intravenous flush.&#xD;
&#xD;
             -  1 mg adrenaline will be injected at t = 7 minutes, the injection will be repeated&#xD;
                every 5 minutes until return of spontaneous circulation or ending of the&#xD;
                resuscitation decided by the emergency physician.&#xD;
&#xD;
             -  an external electric shock (EEC) will be realized at t = 6 minutes when the&#xD;
                electric heart type allows, then external shock will be repeated every 3 minutes&#xD;
                until return of spontaneous circulation or ending of the resuscitation decided by&#xD;
                the emergency physician.&#xD;
&#xD;
           During that resuscitation the following parameters will be collected:&#xD;
&#xD;
             -  The type of cardiac arrest (place of cardiac arrest [home, public place, stadium&#xD;
                …], cardiac arrest before a witness or prompt rescue team, cardiac massage by the&#xD;
                witness or prompt rescue team, durations between collapse and the start of&#xD;
                resuscitation, non-specialized / specialized resuscitation, defibrillation shock by&#xD;
                the witness or prompt rescue team), ETCO2, blood pressure and SpO2.&#xD;
&#xD;
             -  the initial electrical rhythm (defined by ECG) by the mobile intensive care unit&#xD;
                (MICI) and ECG 5 minutes after return of spontaneous circulation.&#xD;
&#xD;
             -  arterial blood gas lactate&#xD;
&#xD;
             -  troponin (24 hours after ROSC)&#xD;
&#xD;
             -  liver function (24 hours after ROSC)&#xD;
&#xD;
             -  creatinine (24 hours after ROSC)&#xD;
&#xD;
             -  echocardiography (4 and 24 hours after ROSC)&#xD;
&#xD;
        4. EXPECTED DURATION OF PARTICIPATION OF PEOPLE AND DESCRIPTION OF THE TIMING AND DURATION&#xD;
           OF THE RESEARCH.&#xD;
&#xD;
           Duration of intervention: 4 minutes Inclusion time: 30 months duration of participation&#xD;
           (+ monitoring treatment): 6 months Total duration of the study: 3 years&#xD;
&#xD;
        5. RANDOMIZATION Randomization will be realized by block and will be stratified by center.&#xD;
           The boxes are numbered and contain drugs specified by the randomization arm.&#xD;
           Randomization will be done by assigning at each inclusion a box taken in order of&#xD;
           increasing numbers of the randomization list. The randomization list will be established&#xD;
           under the responsibility of the clinical research unit.&#xD;
&#xD;
        6. MONITORING COMMITTEE A monitoring committee will conduct an interim analysis after the&#xD;
           inclusion of 50% and 75% of patients and will decide to stop or continue the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Discontinuation of the experimental treatment being tested&#xD;
  </why_stopped>
  <start_date type="Actual">January 2, 2015</start_date>
  <completion_date type="Actual">January 2, 2018</completion_date>
  <primary_completion_date type="Actual">July 2, 2017</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of return of spontaneous circulation (ROSC)</measure>
    <time_frame>at 5 minutes</time_frame>
    <description>Rate of return of spontaneous circulation (ROSC) defined as a central pulse (carotid or femoral) palpable for more than 5 minutes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ETCO2</measure>
    <time_frame>at 0, 5 and 60 minutes</time_frame>
    <description>ETCO2 (before ROSC, 5 and 60 min after ROSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>at 5 and 60 min</time_frame>
    <description>at 5 and 60 min after ROSC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ECG</measure>
    <time_frame>at 0, 5 and 60 minutes</time_frame>
    <description>ECG (before ROSC, 5 min after ROSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SpO2</measure>
    <time_frame>at 0, 5 and 60 minutes</time_frame>
    <description>SpO2 (before ROSC, 5 and 60 min after ROSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arterial blood gases with lactate</measure>
    <time_frame>at 0 and 5 minutes; 1, 4 and 24 hours</time_frame>
    <description>arterial blood gases with lactate (before ROSC, 5 min, 1, 4 and 24 hours after ROSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Troponin</measure>
    <time_frame>at 24 hours</time_frame>
    <description>troponin (24 hours after ROSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver function</measure>
    <time_frame>at 24 hours</time_frame>
    <description>liver function (24 hours after ROSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Creatinine</measure>
    <time_frame>at 24 hours</time_frame>
    <description>creatinine (24 hours after ROSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Echocardiography</measure>
    <time_frame>at 4 and 24 hours</time_frame>
    <description>echocardiography (4 and 24 hours after ROSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>1, 4 and 24 hours, 1 week, 2 weeks, 1 and 6 months</time_frame>
    <description>survival (1, 4 and 24 hours after ROSC, ICU and hospital discharge, 1 and 6 months)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological score</measure>
    <time_frame>1 week, 2 weeks, 1 and 6 months</time_frame>
    <description>neurological score (ICU and hospital discharge, 1 and 6 months)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Cardiopulmonary Arrest</condition>
  <arm_group>
    <arm_group_label>Intervention arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pharmaco- mechanical optimization</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mechanical optimization only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mechanical optimization only</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>pharmaco- mechanical optimization</intervention_name>
    <description>Getting started as soon as possible cardiopulmonary resuscitation (CPR) mechanical ( LUCAS 2) with inspiratory impedance valve ( ResQPOD ) performed according to the 2015 recommendations of the European Resuscitation Council . It will be carried out continuously without a break for control pulse until the first defibrillation attempt.&#xD;
As soon the peripheral intravenous or intraosseous line is set the intervention group will receive an injection of 2 mg of sodium nitroprusside. 4 minutes after the first injection, a second and last injection of 1 mg of sodium nitroprusside will be realized.- The preparation procedure of the sodium nitroprusside will be:&#xD;
Using a &quot;pomping needle&quot; and the provided syringe 4 ml of the solvent (Water for Injections, WFI) will be take.&#xD;
The 4 ml of WFI will be empty in the 50 mg vial of lyophilisate sodium nitroprusside to solubilize the product.&#xD;
Always with the needle and 20 ml syringe, the 4 ml of this solution (50 mg in 4 ml) will be collect.</description>
    <arm_group_label>Intervention arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>mechanical optimization only</intervention_name>
    <description>Getting started as soon as possible cardiopulmonary resuscitation (CPR) mechanical ( LUCAS 2) with inspiratory impedance valve ( ResQPOD ) performed according to the 2015 recommendations of the European Resuscitation Council . It will be carried out continuously without a break for control pulse until the first defibrillation attempt.</description>
    <arm_group_label>Mechanical optimization only</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient with out of hospital cardiac arrest&#xD;
&#xD;
          -  Age&gt; 18 years and &lt;75 years&#xD;
&#xD;
          -  Initial Rhythm: Ventricular fibrillation or ventricular tachycardia or pulseless&#xD;
             electrical activity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  out of hospital cardiac arrest of non-cardiac origin:&#xD;
&#xD;
               -  trauma&#xD;
&#xD;
               -  anoxic, including drowning&#xD;
&#xD;
               -  hemorrhage,&#xD;
&#xD;
               -  overdose (drugs),&#xD;
&#xD;
               -  drug,&#xD;
&#xD;
               -  electric&#xD;
&#xD;
          -  Do Not Resuscitate Order,&#xD;
&#xD;
          -  obvious signs of clinical death (decomposition, cadaveric rigidity, decapitation)&#xD;
&#xD;
          -  recent sternotomy (&lt;6 months or recent scar)&#xD;
&#xD;
          -  Contraindications related to sodium nitroprusside&#xD;
&#xD;
               -  Women of childbearing age (between 18 and 55 years)&#xD;
&#xD;
               -  Other contra-indications will usually not known during resuscitation in case of&#xD;
                  presence of a relative rescue team must be searched: Hypothyroidism, Sulfuryl&#xD;
                  transferase deficiency (rhodanese Lang) currently recognized in patients with&#xD;
                  Leber optic atrophy, tobacco amblyopia or severe hepatic impairment.&#xD;
&#xD;
          -  Obesity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrick PLAISANCE, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SMUR - Hôpital Lariboisière</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Schultz J, Segal N, Kolbeck J, Caldwell E, Thorsgard M, McKnite S, Aufderheide TP, Lurie KG, Yannopoulos D. Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation. Resuscitation. 2011 Dec;82 Suppl 2(0 2):S35-40. doi: 10.1016/S0300-9572(11)70149-6.</citation>
    <PMID>22208176</PMID>
  </reference>
  <reference>
    <citation>Schultz J, Segal N, Kolbeck J, McKnite S, Caldwell E, Yannopoulos D. Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest. Resuscitation. 2012 Mar;83(3):374-7. doi: 10.1016/j.resuscitation.2011.07.038. Epub 2011 Aug 22.</citation>
    <PMID>21864483</PMID>
  </reference>
  <reference>
    <citation>Schultz JC, Segal N, Caldwell E, Kolbeck J, McKnite S, Lebedoff N, Zviman M, Aufderheide TP, Yannopoulos D. Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models. Crit Care Med. 2011 Dec;39(12):2705-10. doi: 10.1097/CCM.0b013e31822668ba.</citation>
    <PMID>21725236</PMID>
  </reference>
  <reference>
    <citation>Yannopoulos D, Matsuura T, Schultz J, Rudser K, Halperin HR, Lurie KG. Sodium nitroprusside enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest. Crit Care Med. 2011 Jun;39(6):1269-74. doi: 10.1097/CCM.0b013e31820ed8a6.</citation>
    <PMID>21358401</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>January 8, 2020</last_update_submitted>
  <last_update_submitted_qc>January 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cardiopulmonary resuscitation</keyword>
  <keyword>Nitroprusside</keyword>
  <keyword>Transthoracic</keyword>
  <keyword>Impedances</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Arrest</mesh_term>
  </condition_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/NCT02225561
org study id: P130946
secondary id: 2014-002010-24
nct id: NCT02225561
lead sponsor: 
has dmc: Yes
Approximately 50,000 patients are victims of out of hospital cardiac arrest every year in
      France. Despite cardiopulmonary resuscitation (CPR) and many studies on the topic
      resuscitation survival after cardiac arrest remains low (1-8%) and has not changed
      significantly over the past five decades.It has recently been shown that the combination of
      different non-invasive therapies, cardiopulmonary resuscitation with mechanical CPR with
      automated compression / decompression and an impedance threshold device, can increase the
      rate of return of spontaneous circulation and short and long term survival after cardiac
      arrest.We propose to study a new cardiopulmonary resuscitation called SNPeCPR (Sodium
      nitroprusside enhanced cardiopulmonary resuscitation), which includes two components:a) a
      mechanical component: cardiopulmonary resuscitation with automated mechanical external chest
      compression and an impedance threshold deviceb) a pharmacological component: sodium
      nitroprusside, an effective arterial vasodilator that decrease vascular resistance, and
      improve flow in vital organs.Our hypothesis is that SNPeCPR should improve the return of
      spontaneous circulation rate during cardiac arrest.
1. OBJECTIVES The objective of this study is to demonstrate the superiority of Sodium
           nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) on optimized standard
           cardiopulmonary resuscitation.

           SNPeCPR includes two components:

             1. a mechanical component: cardiopulmonary resuscitation with automated mechanical
                external chest compression and an impedance threshold device

             2. a pharmacological component: sodium nitroprusside, an effective arterial
                vasodilator that decreasing vascular resistance, facilitates flow elevation in
                vital organs.

           1.1. Main Objective : Assess the interests of the administration of sodium nitroprusside
           during enhanced cardiopulmonary resuscitation.

           1.2. Secondary Objectives : To evaluate the effect of sodium nitroprusside on various
           parameters before and after the return of spontaneous circulation.

           1.3. Outcome Measures : In this declaration, all the criterions measures before ROSC
           have been note as t=0 minute.

           For the elements were the timeframe is a variable, ICU and hospital discharge, they have
           been declare at 1 and 2 weeks respectively.

        2. NAME AND DESCRIPTION OF THE INVESTIGATIONAL DRUG Sodium nitroprusside (SNP) is a potent
           vasodilator that we will use in cardiac arrest to optimize vital organs perfusion. The
           purpose of CPR is to provide oxygenated blood to vital organs that are most susceptible
           to ischemic insult (brain and heart). Since the mechanical combination (cardiopulmonary
           resuscitation with automated mechanical external chest compression and an impedance
           threshold device) provides excellent perfusion pressure, the flow should be optimized
           pharmacological with vasodilation. The SNP reduces arterial vasoconstriction and
           enhances microcirculation. Furthermore, SNP significantly reduces vascular resistance
           and decreases cardiac ejection afterload. Therefore, SNPeCPR can significantly increase
           the flow of blood and optimize carotid and coronary flow.

        3. PROCEDURE During cardiac arrest resuscitation, patients will be included in the study
           after the investigator has verified the inclusion and non-inclusion criterion. A sealed
           box containing SNP or the placebo will then be open in the increasing numbers of
           randomization list.

           Whatever the allocated treatment (nitroprusside or Placebo [5% glucose solution]),
           cardiopulmonary resuscitation protocol will be realize as recommended by the 2010
           European Resuscitation Council and described as follows:

             -  cardiopulmonary resuscitation will be performed continuously without posing for
                control pulse until the first defibrillation attempt. As soon as possible manual
                CPR will be replace by automated mechanical external chest compression (LUCAS® -
                Lund University Cardiopulmonary Assist System) and an impedance threshold device
                (ResQPOD®).

             -  placement of a peripheral intravenous (IV) or intraosseous (IO) line. This
                placement will be privileged to intubation,

             -  when the peripheral intravenous or intraosseous line is set, 1.96 mg sodium
                nitroprusside (SNP) / placebo will be injected, followed by injection of 10 ml
                saline for intravenous flush (t = 0 minutes).

             -  1 mg of epinephrine will be injected at t = 2 minutes,

             -  an external electric shock (EEC) will be realized at t = 3 minutes when the
                electric heart type allows it (ventricular fibrillation or ventricular
                tachycardia),

             -  0.98 mg sodium nitroprusside / placebo will be injected at t = 4 minutes, followed
                by an injection of 10 ml of saline for intravenous flush.

             -  1 mg adrenaline will be injected at t = 7 minutes, the injection will be repeated
                every 5 minutes until return of spontaneous circulation or ending of the
                resuscitation decided by the emergency physician.

             -  an external electric shock (EEC) will be realized at t = 6 minutes when the
                electric heart type allows, then external shock will be repeated every 3 minutes
                until return of spontaneous circulation or ending of the resuscitation decided by
                the emergency physician.

           During that resuscitation the following parameters will be collected:

             -  The type of cardiac arrest (place of cardiac arrest [home, public place, stadium
                …], cardiac arrest before a witness or prompt rescue team, cardiac massage by the
                witness or prompt rescue team, durations between collapse and the start of
                resuscitation, non-specialized / specialized resuscitation, defibrillation shock by
                the witness or prompt rescue team), ETCO2, blood pressure and SpO2.

             -  the initial electrical rhythm (defined by ECG) by the mobile intensive care unit
                (MICI) and ECG 5 minutes after return of spontaneous circulation.

             -  arterial blood gas lactate

             -  troponin (24 hours after ROSC)

             -  liver function (24 hours after ROSC)

             -  creatinine (24 hours after ROSC)

             -  echocardiography (4 and 24 hours after ROSC)

        4. EXPECTED DURATION OF PARTICIPATION OF PEOPLE AND DESCRIPTION OF THE TIMING AND DURATION
           OF THE RESEARCH.

           Duration of intervention: 4 minutes Inclusion time: 30 months duration of participation
           (+ monitoring treatment): 6 months Total duration of the study: 3 years

        5. RANDOMIZATION Randomization will be realized by block and will be stratified by center.
           The boxes are numbered and contain drugs specified by the randomization arm.
           Randomization will be done by assigning at each inclusion a box taken in order of
           increasing numbers of the randomization list. The randomization list will be established
           under the responsibility of the clinical research unit.

        6. MONITORING COMMITTEE A monitoring committee will conduct an interim analysis after the
           inclusion of 50% and 75% of patients and will decide to stop or continue the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Rate of return of spontaneous circulation (ROSC)
time frame: at 5 minutes
description: Rate of return of spontaneous circulation (ROSC) defined as a central pulse (carotid or femoral) palpable for more than 5 minutes
measure: ETCO2
time frame: at 0, 5 and 60 minutes
description: ETCO2 (before ROSC, 5 and 60 min after ROSC)
measure: Blood pressure
time frame: at 5 and 60 min
description: at 5 and 60 min after ROSC
measure: ECG
time frame: at 0, 5 and 60 minutes
description: ECG (before ROSC, 5 min after ROSC)
measure: SpO2
time frame: at 0, 5 and 60 minutes
description: SpO2 (before ROSC, 5 and 60 min after ROSC)
measure: Arterial blood gases with lactate
time frame: at 0 and 5 minutes; 1, 4 and 24 hours
description: arterial blood gases with lactate (before ROSC, 5 min, 1, 4 and 24 hours after ROSC)
measure: Troponin
time frame: at 24 hours
description: troponin (24 hours after ROSC)
measure: Liver function
time frame: at 24 hours
description: liver function (24 hours after ROSC)
measure: Creatinine
time frame: at 24 hours
description: creatinine (24 hours after ROSC)
measure: Echocardiography
time frame: at 4 and 24 hours
description: echocardiography (4 and 24 hours after ROSC)
measure: Survival
time frame: 1, 4 and 24 hours, 1 week, 2 weeks, 1 and 6 months
description: survival (1, 4 and 24 hours after ROSC, ICU and hospital discharge, 1 and 6 months)
measure: Neurological score
time frame: 1 week, 2 weeks, 1 and 6 months
description: neurological score (ICU and hospital discharge, 1 and 6 months)
arm group label: Intervention arm
arm group type: Experimental
description: Pharmaco- mechanical optimization
arm group label: Mechanical optimization only
arm group type: Active Comparator
description: Mechanical optimization only
intervention type: Procedure
intervention name: pharmaco- mechanical optimization
description: Getting started as soon as possible cardiopulmonary resuscitation (CPR) mechanical ( LUCAS 2) with inspiratory impedance valve ( ResQPOD ) performed according to the 2015 recommendations of the European Resuscitation Council . It will be carried out continuously without a break for control pulse until the first defibrillation attempt.
As soon the peripheral intravenous or intraosseous line is set the intervention group will receive an injection of 2 mg of sodium nitroprusside. 4 minutes after the first injection, a second and last injection of 1 mg of sodium nitroprusside will be realized.- The preparation procedure of the sodium nitroprusside will be:
Using a "pomping needle" and the provided syringe 4 ml of the solvent (Water for Injections, WFI) will be take.
The 4 ml of WFI will be empty in the 50 mg vial of lyophilisate sodium nitroprusside to solubilize the product.
Always with the needle and 20 ml syringe, the 4 ml of this solution (50 mg in 4 ml) will be collect.
arm group label: Intervention arm
intervention type: Procedure
intervention name: mechanical optimization only
description: Getting started as soon as possible cardiopulmonary resuscitation (CPR) mechanical ( LUCAS 2) with inspiratory impedance valve ( ResQPOD ) performed according to the 2015 recommendations of the European Resuscitation Council . It will be carried out continuously without a break for control pulse until the first defibrillation attempt.
arm group label: Mechanical optimization only
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Patrick PLAISANCE, MD, PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
citation: Schultz J, Segal N, Kolbeck J, Caldwell E, Thorsgard M, McKnite S, Aufderheide TP, Lurie KG, Yannopoulos D. Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation. Resuscitation. 2011 Dec;82 Suppl 2(0 2):S35-40. doi: 10.1016/S0300-9572(11)70149-6.
PMID: 22208176
citation: Schultz J, Segal N, Kolbeck J, McKnite S, Caldwell E, Yannopoulos D. Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest. Resuscitation. 2012 Mar;83(3):374-7. doi: 10.1016/j.resuscitation.2011.07.038. Epub 2011 Aug 22.
PMID: 21864483
citation: Schultz JC, Segal N, Caldwell E, Kolbeck J, McKnite S, Lebedoff N, Zviman M, Aufderheide TP, Yannopoulos D. Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models. Crit Care Med. 2011 Dec;39(12):2705-10. doi: 10.1097/CCM.0b013e31822668ba.
PMID: 21725236
citation: Yannopoulos D, Matsuura T, Schultz J, Rudser K, Halperin HR, Lurie KG. Sodium nitroprusside enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest. Crit Care Med. 2011 Jun;39(6):1269-74. doi: 10.1097/CCM.0b013e31820ed8a6.
PMID: 21358401
responsible party type: Sponsor
mesh term: Heart Arrest