<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/NCT04494789</url>
  </required_header>
  <id_info>
    <org_study_id>GI-CC35837377</org_study_id>
    <nct_id>NCT04494789</nct_id>
  </id_info>
  <brief_title>Fludrocortisone Dose Response Relationship in Septic Shock - FluDReSS</brief_title>
  <acronym>FluDReSS</acronym>
  <official_title>A Phase II Open Label Randomised Controlled Clinical Trial of Different Dosing Regimens of Fludrocortisone in Septic Shock With Assessment of Temporal Changes in Hormonal, Inflammatory, and Genetic Markers of Vascular Responsiveness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The George Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The George Institute</source>
  <oversight_info>
    <has_dmc>Yes</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 determine the most suitable dose of Fludrocortisone in&#xD;
      reversal of sepsis and shock associated with sepsis in patients who are admitted to the ICU.&#xD;
&#xD;
      The investigators will be looking to see whether patients receiving Fludrocortisone at&#xD;
      different doses recover quicker and spend less time in hospital and in ICU, and to understand&#xD;
      the reasons why this happens at certain doses.&#xD;
&#xD;
      Sepsis is caused by toxic substances (toxins) from bacteria and other organism entering the&#xD;
      bloodstream from a site of infection. In some people, the infection can progress to sepsis&#xD;
      and septic shock where the functions of organs in the body are affected. Patients suffering&#xD;
      from sepsis and septic shock are commonly managed in the intensive care unit (ICU) where they&#xD;
      are prescribed antibiotics as standard therapy, as well as other therapies to support the&#xD;
      functions of the body.&#xD;
&#xD;
      Fludrocortisone is a steroid that has previously shown to be beneficial to help in shock in&#xD;
      patients in ICU, but more information is required about the exact dose that is required to&#xD;
      achieve this. This has been shown by previous research.&#xD;
&#xD;
      However, the exact role of Fludrocortisone and the best dose has not been studied adequately&#xD;
      to date as well as the ways in how it works within the body. The study aims to look tat the&#xD;
      dose and the way it works.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim:&#xD;
&#xD;
        1. To conduct a multi-centre randomised controlled trial to assess the effect of 3&#xD;
           different dose regimens of fludrocortisone on shock reversal in septic shock patients&#xD;
           treated with hydrocortisone.&#xD;
&#xD;
        2. To assess the temporal changes in endocrine inflammatory and gene expression markers in&#xD;
           septic shock patients.&#xD;
&#xD;
      Hypotheses:&#xD;
&#xD;
      In patients with septic shock treated with hydrocortisone,&#xD;
&#xD;
        1. The addition of fludrocortisone to hydrocortisone results in improved vascular&#xD;
           responsiveness to vasopressors as compared to hydrocortisone alone&#xD;
&#xD;
        2. The improvement of vascular responsiveness with fludrocortisone is in a dose dependent&#xD;
           manner&#xD;
&#xD;
        3. Enterally administered fludrocortisone results in adequate plasma level&#xD;
&#xD;
        4. Patients who have early reversal of shock have higher concentrations of, angiotensin II&#xD;
           and angiotensin II-receptor expression and reduced angiotensin converting enzyme 2 (ACE&#xD;
           2) concentrations at baseline and throughout the course of their illness&#xD;
&#xD;
        5. Patients who have early reversal of shock have higher concentrations of plasma free&#xD;
           cortisol, aldosterone and glucocorticoid and mineralocorticoid receptor expression at&#xD;
           baseline and throughout the course of their illness.&#xD;
&#xD;
        6. Patients who demonstrate evidence of both greater angiotensin II and glucocorticoid&#xD;
           receptor expression will have earlier shock reversal than those who have an increase in&#xD;
           expression of either of these receptors.&#xD;
&#xD;
        7. There is a different temporal change in the plasma concentrations and receptor&#xD;
           expression profiles in early shock reversal patients vs. delayed shock reversal&#xD;
           patients.&#xD;
&#xD;
           300 patients will be recruited and randomised to enteral doses of 50mcg fludrocortisone&#xD;
           Q24H, Q12H, Q6H or to the control arm of the study. The study will enrol patients&#xD;
           admitted to a participating intensive care unit and who meet all the inclusion criteria&#xD;
           and no exclusion criteria. Patients in a fludrocortisone arm will receive enteral&#xD;
           fludrocortisone for a maximum of 7 days or until sustained shock reversal or until&#xD;
           discharge from ICU whichever is earlier.&#xD;
&#xD;
           Blood samples acquired will be analysed for:&#xD;
&#xD;
             -  Endocrine - Cortisol, free cortisol, aldosterone and metabolites&#xD;
&#xD;
             -  Inflammatory - Cytokine profiles, markers of vasoplegia&#xD;
&#xD;
             -  Gene Expression - Whole genome RNA sequencing and single cell sequencing&#xD;
&#xD;
             -  To assess the plasma levels following enteral administration of fludrocortisone in&#xD;
                all patients enrolled to undertake detailed analysis of fludrocortisone kinetics in&#xD;
                a subgroup of 30 patients enrolled (10 patients in each dosing group).&#xD;
&#xD;
           For all patients, data will be collected at baseline and daily whilst in the ICU for up&#xD;
           to 8 days. Patients will be followed up to time of discharge from hospital or day 28 if&#xD;
           they are still in hospital, whichever occurs first&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 11, 2021</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 30, 2023</primary_completion_date>
  <phase>Phase 2</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>Time to resolution of shock by Intervention group allocation</measure>
    <time_frame>7 DAYS</time_frame>
    <description>To the assess the time it takes for shock to resolve in each intervention arm</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to resolution of shock and Fludrocortisone Levels</measure>
    <time_frame>7 days</time_frame>
    <description>Assess the levels of fludrocortisone in the interventional groups at time of resolution of shock</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vasopressor Responsiveness by Intervention group allocation</measure>
    <time_frame>7 days</time_frame>
    <description>Area under the curve of vasopressor dose in each intervention arm</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vasopressor Responsiveness and Fludrocortisone Levels</measure>
    <time_frame>7 days</time_frame>
    <description>Area under the curve of vasopressor dose associated with fludrocortisone levels</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrence of shock</measure>
    <time_frame>censored at day 28</time_frame>
    <description>Time between a new episode of shock after reversal of the initial episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilation free days</measure>
    <time_frame>censored at day 28</time_frame>
    <description>Number of Days that are without ventilation during admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU and hospital length of Stay</measure>
    <time_frame>censored at day 28</time_frame>
    <description>Total number of days in ICU and in hospital for the index admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU and hospital mortality</measure>
    <time_frame>censored at day 28</time_frame>
    <description>The number of deaths that are recorded in participants and the location of the deaths when in hospital - ICU or ward. This will include cause of death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delta SOFA Score</measure>
    <time_frame>censored at day 28</time_frame>
    <description>Baseline SOFA score to SOFAmax - numerical calculation based on scoring system of each participant during their admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal SOFA score</measure>
    <time_frame>censored at day 28</time_frame>
    <description>Maximum SOFA score for each participant during their admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Superinfection</measure>
    <time_frame>censored at day 28</time_frame>
    <description>This is the number of new infections that occur &gt;48hrs after commencing study drug</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacokinetic Outcome To assess the plasma levels of enterally administered fludrocortisone in all patients enrolled</measure>
    <time_frame>7 days</time_frame>
    <description>Time to peak concentration of Fludrocortisone</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic Outcomes - To undertake detailed analysis of fludrocortisone kinetics in a subgroup of 30 patients enrolled (10 patients in each dosing group)</measure>
    <time_frame>7 days</time_frame>
    <description>Time to absorption, clearance and metabolism of fludrocortisone in participants in each intervention arm except for the control arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Vascular Responsiveness Analysis</measure>
    <time_frame>7 days</time_frame>
    <description>Acquisition of blood samples at 4 timepoints over the first 7 days or until discharge from ICU for exploratory analysis to assess a range of biomarkers and their interactions with the primary outcomes</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Critically Ill</condition>
  <condition>Septic Shock</condition>
  <arm_group>
    <arm_group_label>Fludrocortisone dosing regime: 24hrs</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Receive 50mcg doses of fludrocortisone every 24hrs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fludrocortisone dosing regime: 12hrs</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Receive 50mcg doses of fludrocortisone every 12hrs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fludrocortisone dosing regime: 6hrs</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Receive 50mcg doses of fludrocortisone every 6hrs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Receives standard treatment without fludrocortisone dosing regime</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludrocortisone Acetate</intervention_name>
    <description>50mcg</description>
    <arm_group_label>Fludrocortisone dosing regime: 24hrs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludrocortisone Acetate</intervention_name>
    <description>100mcg</description>
    <arm_group_label>Fludrocortisone dosing regime: 12hrs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludrocortisone Acetate</intervention_name>
    <description>200mcg</description>
    <arm_group_label>Fludrocortisone dosing regime: 6hrs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard Therapy</intervention_name>
    <description>NO Fludrocortisone</description>
    <arm_group_label>Control Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged 18 years or older&#xD;
&#xD;
          2. Documented site, or strong suspicion of infection with 2 of the 4 clinical signs of&#xD;
             inflammation:&#xD;
&#xD;
               1. Core temperature &gt; 38oC or &lt; 35oC&#xD;
&#xD;
               2. Heart rate &gt; 90bpm&#xD;
&#xD;
               3. Respiratory rate &gt; 20bpm, or PaCO2 &lt; 32mmHg, or mechanical ventilation&#xD;
&#xD;
               4. White cell count &gt; 12 x 109/L or &lt; 4 x 109/L or &gt; 10% immature neutrophils\&#xD;
&#xD;
          3. Being treated with Hydrocortisone at a daily dose of 200mg / day as adjunctive&#xD;
             treatment for sepsis&#xD;
&#xD;
          4. Being treated with mechanical ventilation at the time of randomisation (includes mask&#xD;
             BiPAP/CPAP)&#xD;
&#xD;
          5. Being treated with continuous vasopressors or inotropes to maintain a systolic blood&#xD;
             pressure &gt; 90mmHg, or mean arterial pressure &gt; 60mmHg or a MAP target set by the&#xD;
             treating clinician for maintaining perfusion&#xD;
&#xD;
          6. Administration of vasopressors or inotropes for &gt; 4 hours and present at time of&#xD;
             randomisation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Met all inclusion criteria more than 24 hours ago&#xD;
&#xD;
          2. Patients taking long term corticosteroids or fludrocortisone&#xD;
&#xD;
          3. Patients with systemic fungal infection&#xD;
&#xD;
          4. Death is deemed inevitable or imminent during this admission and either the attending&#xD;
             physician, patient or surrogate legal decision maker is not committed to active&#xD;
             treatment&#xD;
&#xD;
          5. Patient unable to receive enteral medication&#xD;
&#xD;
          6. Death from underlying disease likely within 90 days&#xD;
&#xD;
          7. Patient has been previously enrolled in the study&#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>James Walsham, MB ChB, MRCP, FCICM.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Princess Alexandra Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dorrilyn Rajbhandari</last_name>
    <phone>0410530548</phone>
    <email>drajbhandari@georegeinstitute.org.au</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Naomi Hammond, PhD RN BN MN (Crit. Care) MPH</last_name>
    <email>nhammond@georgeinstitiute.org.au</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Bankstown Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Blacktown Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dhaval Ghelani</last_name>
      <email>Dhaval.Ghelani@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal North Shore Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lachlan Donaldson</last_name>
      <email>ldonaldson@georgeinstitute.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane Women's Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeremy Cohan</last_name>
      <email>cohenjeremy@me.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wesley Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bala Venkatesh</last_name>
      <email>bmvenkat@bigpond.net.au</email>
    </contact>
    <contact_backup>
      <last_name>Jeremy Cohan</last_name>
      <email>cohenjeremy@me.com</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Gold Coast University Hospital</name>
      <address>
        <city>Gold Coast</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>James McCullough</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Mater Misericordiae</name>
      <address>
        <city>Raymond Terrace</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Loki Johnk</last_name>
      <email>Loki.Johnk@mater.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospiital</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>James Walsham, FRANZCA</last_name>
      <email>James.Walsham@health.qld.gov.au</email>
    </contact>
    <investigator>
      <last_name>James Walsham, FRANZCA</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth II Hospital</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra Peake</last_name>
      <email>sandra.peake@sa.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Austin Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rinaldo Bellomo</last_name>
      <email>Rinaldo.BELLOMO@austin.org.au</email>
    </contact>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 19, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>January 10, 2023</last_update_submitted>
  <last_update_submitted_qc>January 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Shock</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fludrocortisone</mesh_term>
  </intervention_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/NCT04494789
org study id: GI-CC35837377
nct id: NCT04494789
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the most suitable dose of Fludrocortisone in
      reversal of sepsis and shock associated with sepsis in patients who are admitted to the ICU.

      The investigators will be looking to see whether patients receiving Fludrocortisone at
      different doses recover quicker and spend less time in hospital and in ICU, and to understand
      the reasons why this happens at certain doses.

      Sepsis is caused by toxic substances (toxins) from bacteria and other organism entering the
      bloodstream from a site of infection. In some people, the infection can progress to sepsis
      and septic shock where the functions of organs in the body are affected. Patients suffering
      from sepsis and septic shock are commonly managed in the intensive care unit (ICU) where they
      are prescribed antibiotics as standard therapy, as well as other therapies to support the
      functions of the body.

      Fludrocortisone is a steroid that has previously shown to be beneficial to help in shock in
      patients in ICU, but more information is required about the exact dose that is required to
      achieve this. This has been shown by previous research.

      However, the exact role of Fludrocortisone and the best dose has not been studied adequately
      to date as well as the ways in how it works within the body. The study aims to look tat the
      dose and the way it works.
Aim:

        1. To conduct a multi-centre randomised controlled trial to assess the effect of 3
           different dose regimens of fludrocortisone on shock reversal in septic shock patients
           treated with hydrocortisone.

        2. To assess the temporal changes in endocrine inflammatory and gene expression markers in
           septic shock patients.

      Hypotheses:

      In patients with septic shock treated with hydrocortisone,

        1. The addition of fludrocortisone to hydrocortisone results in improved vascular
           responsiveness to vasopressors as compared to hydrocortisone alone

        2. The improvement of vascular responsiveness with fludrocortisone is in a dose dependent
           manner

        3. Enterally administered fludrocortisone results in adequate plasma level

        4. Patients who have early reversal of shock have higher concentrations of, angiotensin II
           and angiotensin II-receptor expression and reduced angiotensin converting enzyme 2 (ACE
           2) concentrations at baseline and throughout the course of their illness

        5. Patients who have early reversal of shock have higher concentrations of plasma free
           cortisol, aldosterone and glucocorticoid and mineralocorticoid receptor expression at
           baseline and throughout the course of their illness.

        6. Patients who demonstrate evidence of both greater angiotensin II and glucocorticoid
           receptor expression will have earlier shock reversal than those who have an increase in
           expression of either of these receptors.

        7. There is a different temporal change in the plasma concentrations and receptor
           expression profiles in early shock reversal patients vs. delayed shock reversal
           patients.

           300 patients will be recruited and randomised to enteral doses of 50mcg fludrocortisone
           Q24H, Q12H, Q6H or to the control arm of the study. The study will enrol patients
           admitted to a participating intensive care unit and who meet all the inclusion criteria
           and no exclusion criteria. Patients in a fludrocortisone arm will receive enteral
           fludrocortisone for a maximum of 7 days or until sustained shock reversal or until
           discharge from ICU whichever is earlier.

           Blood samples acquired will be analysed for:

             -  Endocrine - Cortisol, free cortisol, aldosterone and metabolites

             -  Inflammatory - Cytokine profiles, markers of vasoplegia

             -  Gene Expression - Whole genome RNA sequencing and single cell sequencing

             -  To assess the plasma levels following enteral administration of fludrocortisone in
                all patients enrolled to undertake detailed analysis of fludrocortisone kinetics in
                a subgroup of 30 patients enrolled (10 patients in each dosing group).

           For all patients, data will be collected at baseline and daily whilst in the ICU for up
           to 8 days. Patients will be followed up to time of discharge from hospital or day 28 if
           they are still in hospital, whichever occurs first
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to resolution of shock by Intervention group allocation
time frame: 7 DAYS
description: To the assess the time it takes for shock to resolve in each intervention arm
measure: Time to resolution of shock and Fludrocortisone Levels
time frame: 7 days
description: Assess the levels of fludrocortisone in the interventional groups at time of resolution of shock
measure: Vasopressor Responsiveness by Intervention group allocation
time frame: 7 days
description: Area under the curve of vasopressor dose in each intervention arm
measure: Vasopressor Responsiveness and Fludrocortisone Levels
time frame: 7 days
description: Area under the curve of vasopressor dose associated with fludrocortisone levels
measure: Recurrence of shock
time frame: censored at day 28
description: Time between a new episode of shock after reversal of the initial episode
measure: Ventilation free days
time frame: censored at day 28
description: Number of Days that are without ventilation during admission
measure: ICU and hospital length of Stay
time frame: censored at day 28
description: Total number of days in ICU and in hospital for the index admission
measure: ICU and hospital mortality
time frame: censored at day 28
description: The number of deaths that are recorded in participants and the location of the deaths when in hospital - ICU or ward. This will include cause of death
measure: Delta SOFA Score
time frame: censored at day 28
description: Baseline SOFA score to SOFAmax - numerical calculation based on scoring system of each participant during their admission
measure: Maximal SOFA score
time frame: censored at day 28
description: Maximum SOFA score for each participant during their admission
measure: Superinfection
time frame: censored at day 28
description: This is the number of new infections that occur >48hrs after commencing study drug
measure: Pharmacokinetic Outcome To assess the plasma levels of enterally administered fludrocortisone in all patients enrolled
time frame: 7 days
description: Time to peak concentration of Fludrocortisone
measure: Pharmacokinetic Outcomes - To undertake detailed analysis of fludrocortisone kinetics in a subgroup of 30 patients enrolled (10 patients in each dosing group)
time frame: 7 days
description: Time to absorption, clearance and metabolism of fludrocortisone in participants in each intervention arm except for the control arm
measure: Vascular Responsiveness Analysis
time frame: 7 days
description: Acquisition of blood samples at 4 timepoints over the first 7 days or until discharge from ICU for exploratory analysis to assess a range of biomarkers and their interactions with the primary outcomes
arm group label: Fludrocortisone dosing regime: 24hrs
arm group type: Active Comparator
description: Receive 50mcg doses of fludrocortisone every 24hrs
arm group label: Fludrocortisone dosing regime: 12hrs
arm group type: Active Comparator
description: Receive 50mcg doses of fludrocortisone every 12hrs
arm group label: Fludrocortisone dosing regime: 6hrs
arm group type: Active Comparator
description: Receive 50mcg doses of fludrocortisone every 6hrs
arm group label: Control Arm
arm group type: Placebo Comparator
description: Receives standard treatment without fludrocortisone dosing regime
intervention type: Drug
intervention name: Fludrocortisone Acetate
description: 50mcg
arm group label: Fludrocortisone dosing regime: 24hrs
intervention type: Drug
intervention name: Fludrocortisone Acetate
description: 100mcg
arm group label: Fludrocortisone dosing regime: 12hrs
intervention type: Drug
intervention name: Fludrocortisone Acetate
description: 200mcg
arm group label: Fludrocortisone dosing regime: 6hrs
intervention type: Other
intervention name: Standard Therapy
description: NO Fludrocortisone
arm group label: Control Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James Walsham, MB ChB, MRCP, FCICM.
role: Principal Investigator
affiliation: Princess Alexandra Hospital
last name: Dorrilyn Rajbhandari
phone: 0410530548
email: drajbhandari@georegeinstitute.org.au
last name: Naomi Hammond, PhD RN BN MN (Crit. Care) MPH
email: nhammond@georgeinstitiute.org.au
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Australia
responsible party type: Sponsor
mesh term: Shock, Septic
mesh term: Shock
mesh term: Critical Illness
mesh term: Fludrocortisone
sharing ipd: Undecided