<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/NCT03002259</url>
  </required_header>
  <id_info>
    <org_study_id>69</org_study_id>
    <nct_id>NCT03002259</nct_id>
  </id_info>
  <brief_title>Dexamethasone for Cardiac Surgery-II Trial</brief_title>
  <acronym>DECS-II</acronym>
  <official_title>Evaluation of Dexamethasone in Cardiac Surgery Using a Novel Trial Design</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayside Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>UMC Utrecht</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bayside Health</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>
      Background. Numerous studies have investigated high-dose corticosteroids in cardiac surgery,&#xD;
      but with mixed results leading to ongoing variations in practice around the world. The&#xD;
      Dexamethasone for Cardiac Surgery-II Trial (DECS-II) is a study comparing high-dose&#xD;
      dexamethasone with placebo in patients undergoing cardiac surgery.&#xD;
&#xD;
      Methods. We discuss the rationale for conducting DECS-II, a 2800-patient, pragmatic,&#xD;
      multicenter, assessor-blinded, randomized trial in cardiac surgery, and the features of the&#xD;
      DECS-II study design (objectives, end points, target population, balanced clusters based on&#xD;
      practice preference with post-randomization consent, treatments, patient follow-up and&#xD;
      analysis).&#xD;
&#xD;
      Conclusions. The DECS-II Trial will use a novel, efficient trial design to evaluate whether&#xD;
      high-dose dexamethasone has a patient-centered benefit of enhancing recovery and increasing&#xD;
      the number of days at home after cardiac surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      High-dose corticosteroids attenuate the inflammatory response to surgery with CPB and are&#xD;
      commonly used in some countries,but uncommonly in the US, Canada and Australia. Steroids can&#xD;
      reliably attenuate activation of the complement pathways associated with cardiac surgery, but&#xD;
      clinical trials have had mixed results. The current evidence is dominated by the results of&#xD;
      two recent large randomized trials: DECS (n=4,494)6 and SIRS (n=7,507).&#xD;
&#xD;
      Both DECS and SIRS assigned patients undergoing cardiac surgery with CPB to receive either a&#xD;
      high intraoperative dose of steroids (dexamethasone 1 mg/kg, or methylprednisolone 500 mg,&#xD;
      respectively) or placebo. The point estimates of both trials suggested a possible reduction&#xD;
      in serious complications and mortality. Planned subgroup analyses in the DECS trial steroids&#xD;
      reduced the incidence of respiratory failure (3.0 % vs. 4.3%, P=0.02), infection (9.5% vs.&#xD;
      14.8%, P=0.009), and shortened hospital stay (median 8 [7-13] vs. 9 [7-13] days, P=0.009).6&#xD;
      Severe renal failure (need for RRT) was reduced, 0.4% vs. 1.0%, P=0.04.8 But SIRS found&#xD;
      methylprednisolone was associated with a higher incidence of myocardial injury (as measured&#xD;
      by elevation of CK-MB enzyme). Nether trial identified a higher risk of myocardial infarction&#xD;
      (MI). The methylprednisolone-induced elevation of CK-MB may therefore be a class effect.&#xD;
&#xD;
      Another compelling finding in pre-planned subgroup analysis of patient age groups is that&#xD;
      when limiting analysis to those aged less than 75 years in the DECS trial, dexamethasone&#xD;
      reduced the risk of the primary composite endpoint, RR 0.74 (95% CI: 0.58-0.95), P=0.017; as&#xD;
      well as respiratory failure RR 0.62 (95% CI: 0.42-0.91), P=0.014; and possibly mortality RR&#xD;
      0.53 (95% CI: 0.26-1.10), P=0.08.6 This age-interaction effect is supported by the&#xD;
      demonstration of increased C-reactive protein concentrations in younger patients enrolled in&#xD;
      the DECS trial.&#xD;
&#xD;
      Therefore, it is highly plausible that prophylactic steroids can suppress deregulated&#xD;
      inflammation and thus improve outcomes in cardiac surgery, but only when used in a less&#xD;
      elderly (i.e. &lt;75 years) patient population.&#xD;
&#xD;
      In retrospect, the primary endpoints of both DECS and SIRS trials can be challenged, in that&#xD;
      they used composites heavily weighted by thrombotic events (MI, stroke) and not specific to&#xD;
      inflammation (respiratory failure, kidney injury, sepsis, prolonged ICU and hospital stay,&#xD;
      mortality). We thus plan to re-evaluate dexamethasone in cardiac surgery, using a&#xD;
      patient-centred, clinically important endpoint focused on enhanced recovery and earlier&#xD;
      hospital discharge: &quot;days alive and at home up to 30 days after surgery&quot;.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 1, 2018</start_date>
  <completion_date type="Anticipated">January 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2023</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>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>days at home up to 30 days after surgery</measure>
    <time_frame>30 days from Start of Surgery</time_frame>
    <description>Home is defined as a person's usual abode or that of a close relative, excluding any nursing facility (rehabilitation center or nursing home).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>respiratory failure</measure>
    <time_frame>30 days from Start of Surgery</time_frame>
    <description>Uninterrupted postoperative mechanical ventilation for more than 48 hours from admission to ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infection</measure>
    <time_frame>30 days from Start of Surgery</time_frame>
    <description>Surgical site infection, pneumonia, or documented positive microbial culture from any site (including blood).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial Infarction</measure>
    <time_frame>30 days from Start of Surgery</time_frame>
    <description>Postoperative myocardial infarction will be defined according to the third universal definition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke</measure>
    <time_frame>30 days from Start of Surgery</time_frame>
    <description>A new neurological deficit lasting more than 24 hours or leading to earlier death, and confirmed by medical imaging.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak blood glucose</measure>
    <time_frame>30 days from Start of Surgery</time_frame>
    <description>The highest blood glucose measured in this same period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay</measure>
    <time_frame>30 days from Start of Surgery</time_frame>
    <description>Time from postoperative ICU admission to ICU discharge (hours) and hospital discharge (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quick SOFA score</measure>
    <time_frame>Each evening on days 1-3 after surgery</time_frame>
    <description>Tachypnoea, altered mentation and/or hypotension</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1956</enrollment>
  <condition>Inflammatory Response</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No placebo required</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dexamethasone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dexamethasone, 1 mg/kg (maximal dose 100 mg), single dose administration before cardiopulmonary bypass</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone administered as a single IV injection after induction of anaesthesia, but before initiation of CPB. Prepare as a 20 mg/mL dexamethasone solution, made up with 0.9% saline to 10 ml.</description>
    <arm_group_label>Dexamethasone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females, age 18 to 75 years undergoing elective cardiac surgery with&#xD;
             cardiopulmonary bypass&#xD;
&#xD;
          2. EuroScore-II estimated risk of 1.5% or higher&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Poor language (English or Dutch) comprehension&#xD;
&#xD;
          2. Type I diabetes&#xD;
&#xD;
          3. Endocarditis or other evidence of sepsis&#xD;
&#xD;
          4. Preoperative steroid therapy&#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>Paul S Myles, MBBS, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Alfred Hospital, Monash University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alfred Health</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>January 9, 2023</last_update_submitted>
  <last_update_submitted_qc>January 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cardiac surgery</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03002259
org study id: 69
nct id: NCT03002259
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Background. Numerous studies have investigated high-dose corticosteroids in cardiac surgery,
      but with mixed results leading to ongoing variations in practice around the world. The
      Dexamethasone for Cardiac Surgery-II Trial (DECS-II) is a study comparing high-dose
      dexamethasone with placebo in patients undergoing cardiac surgery.

      Methods. We discuss the rationale for conducting DECS-II, a 2800-patient, pragmatic,
      multicenter, assessor-blinded, randomized trial in cardiac surgery, and the features of the
      DECS-II study design (objectives, end points, target population, balanced clusters based on
      practice preference with post-randomization consent, treatments, patient follow-up and
      analysis).

      Conclusions. The DECS-II Trial will use a novel, efficient trial design to evaluate whether
      high-dose dexamethasone has a patient-centered benefit of enhancing recovery and increasing
      the number of days at home after cardiac surgery.
High-dose corticosteroids attenuate the inflammatory response to surgery with CPB and are
      commonly used in some countries,but uncommonly in the US, Canada and Australia. Steroids can
      reliably attenuate activation of the complement pathways associated with cardiac surgery, but
      clinical trials have had mixed results. The current evidence is dominated by the results of
      two recent large randomized trials: DECS (n=4,494)6 and SIRS (n=7,507).

      Both DECS and SIRS assigned patients undergoing cardiac surgery with CPB to receive either a
      high intraoperative dose of steroids (dexamethasone 1 mg/kg, or methylprednisolone 500 mg,
      respectively) or placebo. The point estimates of both trials suggested a possible reduction
      in serious complications and mortality. Planned subgroup analyses in the DECS trial steroids
      reduced the incidence of respiratory failure (3.0 % vs. 4.3%, P=0.02), infection (9.5% vs.
      14.8%, P=0.009), and shortened hospital stay (median 8 [7-13] vs. 9 [7-13] days, P=0.009).6
      Severe renal failure (need for RRT) was reduced, 0.4% vs. 1.0%, P=0.04.8 But SIRS found
      methylprednisolone was associated with a higher incidence of myocardial injury (as measured
      by elevation of CK-MB enzyme). Nether trial identified a higher risk of myocardial infarction
      (MI). The methylprednisolone-induced elevation of CK-MB may therefore be a class effect.

      Another compelling finding in pre-planned subgroup analysis of patient age groups is that
      when limiting analysis to those aged less than 75 years in the DECS trial, dexamethasone
      reduced the risk of the primary composite endpoint, RR 0.74 (95% CI: 0.58-0.95), P=0.017; as
      well as respiratory failure RR 0.62 (95% CI: 0.42-0.91), P=0.014; and possibly mortality RR
      0.53 (95% CI: 0.26-1.10), P=0.08.6 This age-interaction effect is supported by the
      demonstration of increased C-reactive protein concentrations in younger patients enrolled in
      the DECS trial.

      Therefore, it is highly plausible that prophylactic steroids can suppress deregulated
      inflammation and thus improve outcomes in cardiac surgery, but only when used in a less
      elderly (i.e. <75 years) patient population.

      In retrospect, the primary endpoints of both DECS and SIRS trials can be challenged, in that
      they used composites heavily weighted by thrombotic events (MI, stroke) and not specific to
      inflammation (respiratory failure, kidney injury, sepsis, prolonged ICU and hospital stay,
      mortality). We thus plan to re-evaluate dexamethasone in cardiac surgery, using a
      patient-centred, clinically important endpoint focused on enhanced recovery and earlier
      hospital discharge: "days alive and at home up to 30 days after surgery".
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: days at home up to 30 days after surgery
time frame: 30 days from Start of Surgery
description: Home is defined as a person's usual abode or that of a close relative, excluding any nursing facility (rehabilitation center or nursing home).
measure: respiratory failure
time frame: 30 days from Start of Surgery
description: Uninterrupted postoperative mechanical ventilation for more than 48 hours from admission to ICU
measure: Infection
time frame: 30 days from Start of Surgery
description: Surgical site infection, pneumonia, or documented positive microbial culture from any site (including blood).
measure: Myocardial Infarction
time frame: 30 days from Start of Surgery
description: Postoperative myocardial infarction will be defined according to the third universal definition
measure: Stroke
time frame: 30 days from Start of Surgery
description: A new neurological deficit lasting more than 24 hours or leading to earlier death, and confirmed by medical imaging.
measure: Peak blood glucose
time frame: 30 days from Start of Surgery
description: The highest blood glucose measured in this same period
measure: Length of stay
time frame: 30 days from Start of Surgery
description: Time from postoperative ICU admission to ICU discharge (hours) and hospital discharge (days).
measure: Quick SOFA score
time frame: Each evening on days 1-3 after surgery
description: Tachypnoea, altered mentation and/or hypotension
arm group label: Control
arm group type: No Intervention
description: No placebo required
arm group label: Dexamethasone
arm group type: Active Comparator
description: Dexamethasone, 1 mg/kg (maximal dose 100 mg), single dose administration before cardiopulmonary bypass
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone administered as a single IV injection after induction of anaesthesia, but before initiation of CPB. Prepare as a 20 mg/mL dexamethasone solution, made up with 0.9% saline to 10 ml.
arm group label: Dexamethasone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Paul S Myles, MBBS, MD
role: Principal Investigator
affiliation: Alfred Hospital, Monash University
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Dexamethasone
sharing ipd: No