<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/NCT01722422</url>
  </required_header>
  <id_info>
    <org_study_id>PHRC 11-05</org_study_id>
    <nct_id>NCT01722422</nct_id>
  </id_info>
  <brief_title>Hyperoxia and Hypertonic Saline in Septic Shock</brief_title>
  <acronym>Hyper2S</acronym>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Angers</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Angers</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Assessment of the effect of hyperoxia and hypertonic saline on survival in patients with&#xD;
      septic shock Hyperoxia and hypertonic saline may have beneficial effects on organ perfusion&#xD;
      and oxygenation and may reduce the organ failure occurences. To date, only scarce data are&#xD;
      available. Side effects are not well described. Therefore we designed a randomized clinical&#xD;
      trial in order to assess the early administration of hypertonic saline and oxygen in the very&#xD;
      early beginning of septic shock.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is designed as factorial 2x2. Patients will be stratified at the randomisation&#xD;
      according the presence or absence of Acute Respiratory Distress Syndrome in order to perform&#xD;
      a sub group analysis for all outcome criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</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>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>all-cause mortality</measure>
    <time_frame>day 28</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>all-cause mortality</measure>
    <time_frame>day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evolution of organ failures</measure>
    <time_frame>day 1 to day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>catecholamines free days</measure>
    <time_frame>day 1 to day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mechanical ventilation free days</measure>
    <time_frame>day 1 to day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>safety data</measure>
    <time_frame>day 1 to day 90</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">441</enrollment>
  <condition>Septic Shock</condition>
  <condition>Adult Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>normoxia and isotonic saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Administration of oxygen in order to maintain SaO2 between 88% and 95%. Fluid resuscitation if needed with isotonic saline during 3 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>normoxia and 3% hypertonic saline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of oxygen in order to maintain SaO2 between 88% and 95%. Fluid resuscitation if needed with 3% hypertonic saline during 3 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hyperoxia and isotonic saline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of oxygen with FiO2 = 100% during the first 24 hours and after switch oxygen administration to usual care.&#xD;
Fluid resuscitation if needed with isotonic saline during 3 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hyperoxia and 3% hypertonic saline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of oxygen with FiO2 = 100% during the first 24 hours and after switch oxygen administration to usual care.&#xD;
Fluid resuscitation if needed with 3% hypertonic saline during 3 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oxygen and saline</intervention_name>
    <arm_group_label>hyperoxia and 3% hypertonic saline</arm_group_label>
    <arm_group_label>hyperoxia and isotonic saline</arm_group_label>
    <arm_group_label>normoxia and 3% hypertonic saline</arm_group_label>
    <arm_group_label>normoxia and isotonic saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with less than 6 hours septic shock according criteria of Bone&#xD;
&#xD;
          -  minimal dose of catecholamines at least 0.1 µg/Kg/min&#xD;
&#xD;
          -  patient with mechanical ventilation&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt; 18 years&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  participation in other trial with the same endpoint&#xD;
&#xD;
          -  moribund&#xD;
&#xD;
          -  absence of registration in french health care system&#xD;
&#xD;
          -  patient protected by law&#xD;
&#xD;
          -  hypernatremia &lt; 130 mmol/l ou &gt; 145 mmol/l&#xD;
&#xD;
          -  patient with P/F &lt; 100 mm Hg with PEEP &gt; 5 cms of water&#xD;
&#xD;
          -  intracranial hypertension&#xD;
&#xD;
          -  patient admitted for cardiac arrest&#xD;
&#xD;
          -  overt cardiac failure&#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>University Hospital Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Calzia E, Asfar P, Hauser B, Matejovic M, Ballestra C, Radermacher P, Georgieff M. Hyperoxia may be beneficial. Crit Care Med. 2010 Oct;38(10 Suppl):S559-68. doi: 10.1097/CCM.0b013e3181f1fe70.</citation>
    <PMID>21164398</PMID>
  </reference>
  <reference>
    <citation>Goertz AW, Mehl T, Lindner KH, Rockemann MG, Schirmer U, Schwilk B, Georgieff M. Effect of 7.2% hypertonic saline/6% hetastarch on left ventricular contractility in anesthetized humans. Anesthesiology. 1995 Jun;82(6):1389-95. doi: 10.1097/00000542-199506000-00010.</citation>
    <PMID>7540812</PMID>
  </reference>
  <reference>
    <citation>Oliveira RP, Weingartner R, Ribas EO, Moraes RS, Friedman G. Acute haemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis. Intensive Care Med. 2002 Nov;28(11):1574-81. doi: 10.1007/s00134-002-1509-x. Epub 2002 Oct 1.</citation>
    <PMID>12415443</PMID>
  </reference>
  <reference>
    <citation>Junger WG, Hoyt DB, Davis RE, Herdon-Remelius C, Namiki S, Junger H, Loomis W, Altman A. Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38. J Clin Invest. 1998 Jun 15;101(12):2768-79. doi: 10.1172/JCI1354.</citation>
    <PMID>9637711</PMID>
  </reference>
  <reference>
    <citation>Coimbra R, Hoyt DB, Junger WG, Angle N, Wolf P, Loomis W, Evers MF. Hypertonic saline resuscitation decreases susceptibility to sepsis after hemorrhagic shock. J Trauma. 1997 Apr;42(4):602-6; discussion 606-7. doi: 10.1097/00005373-199704000-00004.</citation>
    <PMID>9137245</PMID>
  </reference>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>November 19, 2014</last_update_submitted>
  <last_update_submitted_qc>November 19, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 20, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sepsis</keyword>
  <keyword>shock</keyword>
  <keyword>hyperoxia</keyword>
  <keyword>hypertonic saline</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Shock</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/NCT01722422
org study id: PHRC 11-05
nct id: NCT01722422
lead sponsor: 
has dmc: Yes
Assessment of the effect of hyperoxia and hypertonic saline on survival in patients with
      septic shock Hyperoxia and hypertonic saline may have beneficial effects on organ perfusion
      and oxygenation and may reduce the organ failure occurences. To date, only scarce data are
      available. Side effects are not well described. Therefore we designed a randomized clinical
      trial in order to assess the early administration of hypertonic saline and oxygen in the very
      early beginning of septic shock.
The study is designed as factorial 2x2. Patients will be stratified at the randomisation
      according the presence or absence of Acute Respiratory Distress Syndrome in order to perform
      a sub group analysis for all outcome criteria.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: all-cause mortality
time frame: day 28
measure: all-cause mortality
time frame: day 90
measure: evolution of organ failures
time frame: day 1 to day 28
measure: catecholamines free days
time frame: day 1 to day 28
measure: mechanical ventilation free days
time frame: day 1 to day 28
measure: safety data
time frame: day 1 to day 90
arm group label: normoxia and isotonic saline
arm group type: Placebo Comparator
description: Administration of oxygen in order to maintain SaO2 between 88% and 95%. Fluid resuscitation if needed with isotonic saline during 3 days.
arm group label: normoxia and 3% hypertonic saline
arm group type: Active Comparator
description: Administration of oxygen in order to maintain SaO2 between 88% and 95%. Fluid resuscitation if needed with 3% hypertonic saline during 3 days.
arm group label: hyperoxia and isotonic saline
arm group type: Active Comparator
description: Administration of oxygen with FiO2 = 100% during the first 24 hours and after switch oxygen administration to usual care.
Fluid resuscitation if needed with isotonic saline during 3 days.
arm group label: hyperoxia and 3% hypertonic saline
arm group type: Active Comparator
description: Administration of oxygen with FiO2 = 100% during the first 24 hours and after switch oxygen administration to usual care.
Fluid resuscitation if needed with 3% hypertonic saline during 3 days.
intervention type: Drug
intervention name: oxygen and saline
arm group label: hyperoxia and 3% hypertonic saline
arm group label: hyperoxia and isotonic saline
arm group label: normoxia and 3% hypertonic saline
arm group label: normoxia and isotonic saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
citation: Calzia E, Asfar P, Hauser B, Matejovic M, Ballestra C, Radermacher P, Georgieff M. Hyperoxia may be beneficial. Crit Care Med. 2010 Oct;38(10 Suppl):S559-68. doi: 10.1097/CCM.0b013e3181f1fe70.
PMID: 21164398
citation: Goertz AW, Mehl T, Lindner KH, Rockemann MG, Schirmer U, Schwilk B, Georgieff M. Effect of 7.2% hypertonic saline/6% hetastarch on left ventricular contractility in anesthetized humans. Anesthesiology. 1995 Jun;82(6):1389-95. doi: 10.1097/00000542-199506000-00010.
PMID: 7540812
citation: Oliveira RP, Weingartner R, Ribas EO, Moraes RS, Friedman G. Acute haemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis. Intensive Care Med. 2002 Nov;28(11):1574-81. doi: 10.1007/s00134-002-1509-x. Epub 2002 Oct 1.
PMID: 12415443
citation: Junger WG, Hoyt DB, Davis RE, Herdon-Remelius C, Namiki S, Junger H, Loomis W, Altman A. Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38. J Clin Invest. 1998 Jun 15;101(12):2768-79. doi: 10.1172/JCI1354.
PMID: 9637711
citation: Coimbra R, Hoyt DB, Junger WG, Angle N, Wolf P, Loomis W, Evers MF. Hypertonic saline resuscitation decreases susceptibility to sepsis after hemorrhagic shock. J Trauma. 1997 Apr;42(4):602-6; discussion 606-7. doi: 10.1097/00005373-199704000-00004.
PMID: 9137245
responsible party type: Sponsor
mesh term: Shock, Septic
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Shock