<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/NCT02186951</url>
  </required_header>
  <id_info>
    <org_study_id>I13018 ANTHARTIC</org_study_id>
    <nct_id>NCT02186951</nct_id>
  </id_info>
  <brief_title>Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications</brief_title>
  <acronym>ANTHARTIC</acronym>
  <official_title>Prevention of Early Ventilator-associated Pneumonia With Antibiotic Therapy in Patients Treated With Mild Therapeutic Hypothermia After Cardiac Arrest.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Limoges</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Limoges</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Mild therapeutic hypothermia is currently recommended in management of cardiac arrests with&#xD;
      shockable rhythm. In mechanically ventilated patients who were resuscitated after&#xD;
      out-of-hospital cardiac arrests, mild therapeutic hypothermia side effects are conductive for&#xD;
      infectious complications and especially for ventilator-associated pneumonia (VAP).&#xD;
&#xD;
      Despite high incidence of VAP and other infectious complications, it is not currently&#xD;
      recommended to use antibiotic prophylaxis on the responsible germs. Yet VAP incidence could&#xD;
      be decreased if an antibiotic therapy was systematically given to patient treated with mild&#xD;
      therapeutic hypothermia after a cardiac arrest. Several retrospective studies showed less&#xD;
      infectious complications but also decreased morbidity and mortality related to these&#xD;
      complications when antibiotic therapy was given early to patients treated with therapeutic&#xD;
      hypothermia after cardiac arrest.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicenter add-on randomized controlled double-blind trial assessing the efficacy of&#xD;
      preventive antibiotics amoxicillin-clavulanic acid vs placebo to prevent occurrence of early&#xD;
      VAP after out-of-hospital cardiac arrest receiving mild therapeutic hypothermia, in addition&#xD;
      to usual VAP prevention measures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 18, 2014</start_date>
  <completion_date type="Actual">September 14, 2017</completion_date>
  <primary_completion_date type="Actual">October 27, 2016</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence reduction of early VAP</measure>
    <time_frame>7 days</time_frame>
    <description>Incidence reduction of early VAP with short term amoxicillin-clavulanic acid in patients treated with hypothermia after out-of-hospital cardiac arrest</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>28 days</time_frame>
    <description>Mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early nosocomial infectious complications</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">197</enrollment>
  <condition>Ventilator-associated Pneumonia</condition>
  <condition>Cardiac Arrests With Shockable Rhythm</condition>
  <condition>Mild Therapeutic Hypothermia</condition>
  <condition>Preventive Antibiotics</condition>
  <arm_group>
    <arm_group_label>Amoxicillin clavulanic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amoxicillin - clavulanic acid</intervention_name>
    <description>Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.</description>
    <arm_group_label>Amoxicillin clavulanic acid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Older than 18 years-old, intubated and mechanically ventilated after out-of-hospital&#xD;
             resuscitated cardiac arrest secondary to shockable rhythm&#xD;
&#xD;
          -  Hospitalized in an ICU&#xD;
&#xD;
          -  Mild therapeutic hypothermia procedure (32° to 35°C) scheduled (24 to 36 hours)&#xD;
&#xD;
          -  Delay from ROSC to randomisation &lt; 6 hours&#xD;
&#xD;
          -  Consent from family members or emergency consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Out-of-hospital cardiac arrest secondary to non shockable rhythm and In-hospital&#xD;
             cardiac arrest&#xD;
&#xD;
          -  Need for cardiac support by cardiopulmonary bypass&#xD;
&#xD;
          -  Ongoing antibiotic therapy or during the week before&#xD;
&#xD;
          -  Ongoing or concomitant pneumonia&#xD;
&#xD;
          -  Known chronic colonization with MRB&#xD;
&#xD;
          -  Hypersensitivity to the active substances, to any of the penicillins or to any of the&#xD;
             excipients.&#xD;
&#xD;
          -  History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another&#xD;
             beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).&#xD;
&#xD;
          -  History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid, according&#xD;
             to the latest version of the SmPC.&#xD;
&#xD;
          -  Previous lung disease&#xD;
&#xD;
          -  Predictable decision of early care limitation&#xD;
&#xD;
          -  Patient under guardianship or curatorship&#xD;
&#xD;
          -  Moribund patient&#xD;
&#xD;
          -  Participation to another trial within 30 days&#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>Bruno FRANCOIS, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Limoges UH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CH Angouleme - Service de Réanimation</name>
      <address>
        <city>Angoulême</city>
        <state>Saint Michel</state>
        <zip>16470</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Argenteuil - Service de Réanimation</name>
      <address>
        <city>Argenteuil</city>
        <zip>95107</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Brive La Gaillarde - Service de Réanimation</name>
      <address>
        <city>Brive La Gaillarde</city>
        <zip>19100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Dijon - Serve de Réanimation</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP - Hôpital pointcaré - Service de Réanimation</name>
      <address>
        <city>Garches</city>
        <zip>92380</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH du MANS</name>
      <address>
        <city>Le Mans</city>
        <zip>72000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Limoges - Service de réanimation polyvalente</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes - Service de réanimation</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Orléans - service de Réanimation</name>
      <address>
        <city>Orleans</city>
        <zip>47067</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP - Hôpital Lariboisière - Service de Réanimation</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP - Hôpital Cochin - Service de Réanimation</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Périgueux</name>
      <address>
        <city>Perigueux</city>
        <zip>24019</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Strasbourg - service de Réanimation</name>
      <address>
        <city>Strasbourg</city>
        <zip>67000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Tours - Service de Réanimation</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Versailles - service de Réanimation</name>
      <address>
        <city>Versailles</city>
        <zip>78000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>Francois B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefeve G, Quenot JP, Desachy A, Kamel T, Bedon-Carte S, Diehl JL, Chudeau N, Karam E, Durand-Zaleski I, Giraudeau B, Vignon P, Le Gouge A; CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. doi: 10.1056/NEJMoa1812379.</citation>
    <PMID>31693806</PMID>
  </results_reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>March 16, 2020</last_update_submitted>
  <last_update_submitted_qc>March 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ventilator-associated pneumonia</keyword>
  <keyword>cardiac arrests with shockable rhythm</keyword>
  <keyword>Mild therapeutic hypothermia</keyword>
  <keyword>preventive antibiotics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Pneumonia, Ventilator-Associated</mesh_term>
    <mesh_term>Heart Arrest</mesh_term>
    <mesh_term>Hypothermia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Clavulanic Acids</mesh_term>
    <mesh_term>Clavulanic Acid</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/NCT02186951
org study id: I13018 ANTHARTIC
nct id: NCT02186951
lead sponsor: 
has dmc: No
Mild therapeutic hypothermia is currently recommended in management of cardiac arrests with
      shockable rhythm. In mechanically ventilated patients who were resuscitated after
      out-of-hospital cardiac arrests, mild therapeutic hypothermia side effects are conductive for
      infectious complications and especially for ventilator-associated pneumonia (VAP).

      Despite high incidence of VAP and other infectious complications, it is not currently
      recommended to use antibiotic prophylaxis on the responsible germs. Yet VAP incidence could
      be decreased if an antibiotic therapy was systematically given to patient treated with mild
      therapeutic hypothermia after a cardiac arrest. Several retrospective studies showed less
      infectious complications but also decreased morbidity and mortality related to these
      complications when antibiotic therapy was given early to patients treated with therapeutic
      hypothermia after cardiac arrest.
Multicenter add-on randomized controlled double-blind trial assessing the efficacy of
      preventive antibiotics amoxicillin-clavulanic acid vs placebo to prevent occurrence of early
      VAP after out-of-hospital cardiac arrest receiving mild therapeutic hypothermia, in addition
      to usual VAP prevention measures.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incidence reduction of early VAP
time frame: 7 days
description: Incidence reduction of early VAP with short term amoxicillin-clavulanic acid in patients treated with hypothermia after out-of-hospital cardiac arrest
measure: Mortality
time frame: 28 days
description: Mortality
measure: Early nosocomial infectious complications
time frame: 28 days
arm group label: Amoxicillin clavulanic acid
arm group type: Experimental
description: Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
intervention type: Drug
intervention name: Amoxicillin - clavulanic acid
description: Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
arm group label: Amoxicillin clavulanic acid
intervention type: Drug
intervention name: Placebo
description: Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bruno FRANCOIS, MD
role: Principal Investigator
affiliation: Limoges UH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
citation: Francois B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefeve G, Quenot JP, Desachy A, Kamel T, Bedon-Carte S, Diehl JL, Chudeau N, Karam E, Durand-Zaleski I, Giraudeau B, Vignon P, Le Gouge A; CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. doi: 10.1056/NEJMoa1812379.
PMID: 31693806
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Pneumonia, Ventilator-Associated
mesh term: Heart Arrest
mesh term: Hypothermia
mesh term: Amoxicillin
mesh term: Clavulanic Acids
mesh term: Clavulanic Acid