<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/NCT04492280</url>
  </required_header>
  <id_info>
    <org_study_id>176/2018</org_study_id>
    <nct_id>NCT04492280</nct_id>
  </id_info>
  <brief_title>Evaluation of the Role of Hydrocortisone Either Alone or Combined With Fludrocortisone in the Outcome of Septic Shock in Adults</brief_title>
  <official_title>Evaluation of the Role of Hydrocortisone Either Alone or Combined With Fludrocortisone in the Outcome of Septic Shock in Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ain Shams University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ain Shams University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      During Infection, oflfending microbes interact with the host immune system producing a&#xD;
      downstream inflammatory cascade involving cytokines and other mediators, which in turn&#xD;
      triggers a systemic response. The resultant effects linclude vasodilation, increased vascular&#xD;
      permeability, myocardial depression, and impairment of the coagulation cascade, resulting in&#xD;
      global imbalance of systemic oxygen supply and demand. During the late stage of sepsis,&#xD;
      immunosuppression predominates, leading to multi-organ dysfunction and further clinical&#xD;
      deterioration .&#xD;
&#xD;
      Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host&#xD;
      response to infection with two or three on Quick Sepsis-related organ failure assessment&#xD;
      score (qSOFA). Septic shock is defined as the presence of sepsis and refractory hypotension&#xD;
      to fluid management. Vasopressors are needed to maintain systolic blood pressure more than&#xD;
      90mmHg or mean blood pressure more than 65 mmHg .&#xD;
&#xD;
      Experimental and Clinical evidence suggests that sepsis is associated with dysregulated&#xD;
      response of Hypothalamic-pituitary-adrenal axis that may involve any of the steps from&#xD;
      cortisol production to cortisol use by cells .&#xD;
&#xD;
      Glucocorticoid therapy for the treatment of septic shock remains controversial, with&#xD;
      conflicting evidence regarding a mortality benefit. It has been used in patients with septic&#xD;
      shock who remained hypotensive after fluid and vasopressor resuscitation.&#xD;
&#xD;
      Fludrocortisone is a corticosteroid and acts as a powerful mineralocorticoid along with some&#xD;
      additional but comparatively very weak glucocorticoid activity. Relative to cortisol, it is&#xD;
      to 10 times the glucocorticoid potency but 250 to 800 times the mineralocorticoid potency .&#xD;
&#xD;
      Fludrocortisone is added to hydrocortisone to provide additional mineralocorticoid potency.&#xD;
      The rationale for adding mineralocorticoid treatment is that an experimental sepsis study&#xD;
      showed marked nuclear factor NF-κB mediated down regulation of vascular mineralocorticoid&#xD;
      receptors .&#xD;
&#xD;
      Corticosteroids attenuate inflammation in various organs an effect partly related to&#xD;
      inhibition of nuclear factor NF-κB. Improve cardiovascular function by restoring effective&#xD;
      blood volume through increased mineralocorticoid activity and by increasing systemic vascular&#xD;
      resistance through vascular α-Adrenergic responsiveness and reduces inflammation-mediated&#xD;
      vasodilation .&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2018</start_date>
  <completion_date type="Actual">September 1, 2019</completion_date>
  <primary_completion_date type="Actual">September 1, 2019</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>• Mortality rate due to septic shock as a cause.</measure>
    <time_frame>one year</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Septic Shock</condition>
  <arm_group>
    <arm_group_label>1. Group H</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>These patients will receive standard therapy for sepsis plus Hydrocortisone (Solucortef®, E.I.P.I.co. under license of Pfizer) at dose 50mg every 6 hours by Intra venous route.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2. Group HF</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>These patients will receive standard therapy for sepsis plus Hydrocortisone (Solucortef®) at dose of 50mg every 6 hours by Intra venous route and Fludrocortisone (Cortilon®, Amoun) 50 Microgram once daily by nasogastric tube for one week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3. Group C</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>These patients will receive standard therapy for sepsis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrocortisone</intervention_name>
    <description>After approval of the ethical committee of faculty of Medicine Ain Shams University and obtaining a written informed consent from all patients or their legal guardians, the study will be conducted on 66 patients subdivided randomly via computer closed envelopes method into 3 equal groups, 22 patients for each group; group HF (hydrocortisone &amp; fludrocortisone), group H (hydrocortisone) and group C (control group).</description>
    <arm_group_label>1. Group H</arm_group_label>
    <arm_group_label>2. Group HF</arm_group_label>
    <arm_group_label>3. Group C</arm_group_label>
    <other_name>Fludrocortisone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  This study will be conducted on patients between 18-80 years old, both sexes who are&#xD;
             suffering from septic shock and have any of the following any of 1, 2, or 3 criteria&#xD;
&#xD;
          -  CLINICAL EVIDENCE OF INFECTION WITHIN THE PREVIOUS 72 HOURS OF ICU ADMISSION (any of&#xD;
             a, b, or c)&#xD;
&#xD;
               1. Presence of polymorphonuclear cells in a normally sterile body fluid.&#xD;
&#xD;
               2. Culture or Gram stain of blood, sputum, urine or normally sterile body fluid&#xD;
                  positive for a pathogenic micro-organism.&#xD;
&#xD;
               3. Focus of infection identified by visual inspection (e.g. ruptured bowel with the&#xD;
                  presence of free air or bowel contents in the abdomen found at the time of&#xD;
                  surgery, wound with purulent drainage).&#xD;
&#xD;
          -  Sepsis-related organ failure assessment (SOFA) score of 3 or 4 (on a scale of 0 to 4&#xD;
             for each of six organ systems) for at least 2 organs and at least 6 hours (Singer et&#xD;
             al., 2016).&#xD;
&#xD;
          -  Vasopressors Therapy ( norepinephrine , epinephrine , or any other vasopressors at a&#xD;
             dose of ≥ 0.25 µg / kg / minute ) for at least 6 hours to maintain a systolic blood&#xD;
             pressure of at least 90 mm Hg or mean blood pressure of at least 65 mm Hg (Singer et&#xD;
             al., 2016).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal of patient or legal guardian to consent to participate in the study.&#xD;
&#xD;
          -  Pregnancy and lactation.&#xD;
&#xD;
          -  Gastrointestinal Bleeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mona A Ammar</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ain Shams University</investigator_affiliation>
    <investigator_full_name>Mona Ammar</investigator_full_name>
    <investigator_title>Assistant Professor of Anesthesia and Intensive Care</investigator_title>
  </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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrocortisone</mesh_term>
    <mesh_term>Fludrocortisone</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/NCT04492280
org study id: 176/2018
nct id: NCT04492280
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
During Infection, oflfending microbes interact with the host immune system producing a
      downstream inflammatory cascade involving cytokines and other mediators, which in turn
      triggers a systemic response. The resultant effects linclude vasodilation, increased vascular
      permeability, myocardial depression, and impairment of the coagulation cascade, resulting in
      global imbalance of systemic oxygen supply and demand. During the late stage of sepsis,
      immunosuppression predominates, leading to multi-organ dysfunction and further clinical
      deterioration .

      Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host
      response to infection with two or three on Quick Sepsis-related organ failure assessment
      score (qSOFA). Septic shock is defined as the presence of sepsis and refractory hypotension
      to fluid management. Vasopressors are needed to maintain systolic blood pressure more than
      90mmHg or mean blood pressure more than 65 mmHg .

      Experimental and Clinical evidence suggests that sepsis is associated with dysregulated
      response of Hypothalamic-pituitary-adrenal axis that may involve any of the steps from
      cortisol production to cortisol use by cells .

      Glucocorticoid therapy for the treatment of septic shock remains controversial, with
      conflicting evidence regarding a mortality benefit. It has been used in patients with septic
      shock who remained hypotensive after fluid and vasopressor resuscitation.

      Fludrocortisone is a corticosteroid and acts as a powerful mineralocorticoid along with some
      additional but comparatively very weak glucocorticoid activity. Relative to cortisol, it is
      to 10 times the glucocorticoid potency but 250 to 800 times the mineralocorticoid potency .

      Fludrocortisone is added to hydrocortisone to provide additional mineralocorticoid potency.
      The rationale for adding mineralocorticoid treatment is that an experimental sepsis study
      showed marked nuclear factor NF-κB mediated down regulation of vascular mineralocorticoid
      receptors .

      Corticosteroids attenuate inflammation in various organs an effect partly related to
      inhibition of nuclear factor NF-κB. Improve cardiovascular function by restoring effective
      blood volume through increased mineralocorticoid activity and by increasing systemic vascular
      resistance through vascular α-Adrenergic responsiveness and reduces inflammation-mediated
      vasodilation .
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: • Mortality rate due to septic shock as a cause.
time frame: one year
arm group label: 1. Group H
arm group type: Active Comparator
description: These patients will receive standard therapy for sepsis plus Hydrocortisone (Solucortef®, E.I.P.I.co. under license of Pfizer) at dose 50mg every 6 hours by Intra venous route.
arm group label: 2. Group HF
arm group type: Active Comparator
description: These patients will receive standard therapy for sepsis plus Hydrocortisone (Solucortef®) at dose of 50mg every 6 hours by Intra venous route and Fludrocortisone (Cortilon®, Amoun) 50 Microgram once daily by nasogastric tube for one week
arm group label: 3. Group C
arm group type: Placebo Comparator
description: These patients will receive standard therapy for sepsis.
intervention type: Drug
intervention name: Hydrocortisone
description: After approval of the ethical committee of faculty of Medicine Ain Shams University and obtaining a written informed consent from all patients or their legal guardians, the study will be conducted on 66 patients subdivided randomly via computer closed envelopes method into 3 equal groups, 22 patients for each group; group HF (hydrocortisone & fludrocortisone), group H (hydrocortisone) and group C (control group).
arm group label: 1. Group H
arm group label: 2. Group HF
arm group label: 3. Group C
other name: Fludrocortisone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Ain Shams University
investigator full name: Mona Ammar
investigator title: Assistant Professor of Anesthesia and Intensive Care
mesh term: Shock, Septic
mesh term: Shock
mesh term: Hydrocortisone
mesh term: Fludrocortisone