<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/NCT02999386</url>
  </required_header>
  <id_info>
    <org_study_id>14471/14</org_study_id>
    <nct_id>NCT02999386</nct_id>
  </id_info>
  <brief_title>Stress Induced Hyperglycemia In Trauma</brief_title>
  <acronym>SIHG</acronym>
  <official_title>Role Of Stress Induced Hyperglycemia On The Outcome Of Trauma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hamad Medical Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hamad Medical Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The clinical relevance of the observed stress induced hyperglycemia in trauma patients&#xD;
      remains unclear. The earlier studies suggested the implications of cytokines in stress&#xD;
      induced hyperglycemia and the outcomes after trauma. To date, there is little information&#xD;
      available regarding the effect of diabetic hyperglycemia (occult or known) on outcomes after&#xD;
      trauma and whether these patients represent a distinct group with differential outcomes when&#xD;
      compared to those with stress-induced hyperglycemia. Herein, the purpose of this study is to&#xD;
      identify the incidence of stress induced hyperglycemia as well as diabetic hyperglycemia in&#xD;
      trauma patients and to investigate the association between proinflammatory cytokine levels&#xD;
      and hyperglycemia in our trauma population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intensive glucose control is vital for prognosis and preservation of normal physiologic&#xD;
      status in trauma patients. The acute effects of severe trauma, infection, and surgery result&#xD;
      in remarkable metabolic stress on the human body. Hyperglycemia is a normal metabolic&#xD;
      response to stress and injury [1]. Irrespective of the involved injury mechanism,&#xD;
      post-traumatic metabolic changes occur due to stress in terms of an increased glucose&#xD;
      production, decreased insulin production, and insulin resistance in the peripheral tissues&#xD;
      and eventually lead to a state of hyperglycemia. Traumatic injury also induces changes in&#xD;
      endogenous hormone production and enhanced utilization of metabolites that usually lead to&#xD;
      stress related hyperglycemia. Measurement of HbA1c levels can be used as a screening tool to&#xD;
      discriminate unknown diabetes mellitus from stress-induced hyperglycemia (SIH). Published&#xD;
      studies that have evaluated the association between presenting hyperglycemia and worse&#xD;
      outcomes in trauma patients have all consistently showed higher mortality and infection rates&#xD;
      in patients presented with elevated serum glucose levels of 200 mg/dL or more [2-5]. A recent&#xD;
      study evaluated the differential effect of SIH in comparison to diabetic hyperglycemia (DH)&#xD;
      on outcomes in trauma victims. The authors observed that as opposed to DH, SIH is associated&#xD;
      with a higher mortality rate after injury [4]. A prospective study of patients with severe&#xD;
      traumatic brain injury demonstrated that admission glucose levels &gt;11.1 mmol/L were&#xD;
      associated with increased mortality and poor neurologic outcomes [6]. Stress associated with&#xD;
      critical illness is characterized by the activation of inflammatory cellular mediators [7].&#xD;
      During acute illness there is an increase in the systemic inflammatory response that is&#xD;
      characterized by increased production of pro-inflammatory cytokines. Importantly, there is&#xD;
      relationship between abnormal cytokine production and hyperglycemia in severe sepsis patients&#xD;
      which aggravates the immune response leading to poor clinical outcomes. Recent studies&#xD;
      suggested that interleukin-6 (IL-6) is involved in glucose metabolism and insulin action. The&#xD;
      proinflammatory IL-6 is normally released upon infection; however, it induces insulin&#xD;
      resistance during conditions of hyperglycemia [8]. Moreover, IL-18 levels are significantly&#xD;
      elevated in diabetic patients with microalbuminuria as compared with patients with&#xD;
      normoalbuminuria [9]. This might indicate that certain interleukins (IL) are involved in the&#xD;
      pathogenesis of SIH. Though, the clinical relevance of the observed SIH in trauma patients&#xD;
      remains unclear. The earlier studies suggested the implications of cytokines in SIH and&#xD;
      outcomes after trauma. To date, there is little information regarding the effect of diabetic&#xD;
      hyperglycemia (occult or known) on the clinical outcomes after trauma and whether these&#xD;
      patients represent a distinct group with differential outcomes when compared to those with&#xD;
      SIH. The purpose of this study is to identify the incidence of SIH as well as diabetic&#xD;
      hyperglycemia in trauma patients and to investigate the association between the&#xD;
      proinflammatory cytokine levels and hyperglycemia in trauma population.&#xD;
&#xD;
      Primary objective:&#xD;
&#xD;
      - To evaluate the outcomes of stress induced hyperglycemia in patients presented with&#xD;
      traumatic injury.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        -  To investigate the association between pro-inflammatory cytokine levels and SIH in&#xD;
           trauma patients.&#xD;
&#xD;
        -  To identify the incidence of SIH and occult diabetes mellitus in trauma population.&#xD;
&#xD;
      It is a prospective study which will include all adult trauma patients who require hospital&#xD;
      admission and have been investigated for random plasma glucose level and HbA1C measured&#xD;
      within 5 hours of admission. All trauma patients will undergo thorough clinical assessment&#xD;
      and resuscitation according to the Advanced Trauma Life Support (ATLS) guidelines. The&#xD;
      present study will screen all traumatic injury patients presented to the trauma room and&#xD;
      those who are willing to participate and provide written informed consent or consented by the&#xD;
      relatives or used emergency consent (Exception from Informed Consent Requirements for&#xD;
      Emergency Research&quot; Policy # 11026) to draw blood for the investigations will be included in&#xD;
      the study. All the study subjects will be managed according to the standard care of the&#xD;
      hospital. The investigators will directly access all adult traumatic injury patients that&#xD;
      will be presented to the trauma room and review the medical file and/or electronic medical&#xD;
      record (EMR) to confirm the eligibility. Usually trauma patients are unconscious, under shock&#xD;
      and are physically and mentally unfit to communicate or sign consent. The trauma surgeon will&#xD;
      explain the consent form to the legal representatives of the subjects in a separate chamber&#xD;
      in the ICU or in private room in the clinic.&#xD;
&#xD;
      Consent and recruitment procedures will be done in such a way that it will not be disclosed&#xD;
      to other patients in the trauma room or in the ward. The information regarding patient's&#xD;
      enrollment will be kept confidential and all study related interactions with the&#xD;
      subject/patient's legal representative will be done in isolated room in the wards or in the&#xD;
      clinics to maintain complete privacy. To safeguards the severe trauma patients, informed&#xD;
      consent will be taken to participate in research by a legally authorized representative on&#xD;
      behalf of a cognitively impaired subject. In absence of any legally authorized&#xD;
      representative, the investigators will use emergency consent (Exception from Informed Consent&#xD;
      Requirements for Emergency Research&quot; Policy # 11026).&#xD;
&#xD;
      Patients who partially recover cognition will be asked to provide Assent and those fully&#xD;
      recovered their cognition to understand the study will be asked for informed consent to&#xD;
      continue participation. For trauma patients who are unconscious, under severe shock and are&#xD;
      physically and mentally unfit to communicate, legally authorized representative will be&#xD;
      identified with the help of patient's attendants. Explaining the consent will take around&#xD;
      half an hour, and if the legal representative consented to allow subject participation within&#xD;
      5 hours of admission, he/she will be enrolled. Since the research investigations needs to be&#xD;
      done during early hours of admission waiting time could be maximum 2-3 hours post admission.&#xD;
      This study did not include any specific procedure which could provide distress to the&#xD;
      participants. And the subject's privacy will be specifically taken care.&#xD;
&#xD;
      Sample size estimation: There is lack of information on the incidence of stress-induced&#xD;
      hyperglycemia among trauma patients in Qatar. However, the current literature reported the&#xD;
      incidence of stress-induced hyperglycemia (≥200 mg/dl) in trauma patients ranges from 10%-17%&#xD;
      for all trauma admissions [3,4]. Therefore, taking the frequency of hyperglycemia to be 15%&#xD;
      with 5% confidence limit and 97% confidence level, a total of 250 consecutive trauma patients&#xD;
      needs to be included in the study. The investigators aim to complete the target of subject&#xD;
      recruitment within 12 months and this research may take 18 months to be completed.&#xD;
&#xD;
      Bio-specimens: The blood specimen for research (10 ml initially after recruitment and 5 ml&#xD;
      after 24 and 48 hours of admission) will be drawn together with the routine blood&#xD;
      investigation.&#xD;
&#xD;
      For each study participant, blood will be drawn on admission to investigate Hemoglobin,&#xD;
      HbA1C, blood glucose levels, Lactate, Base Deficit, High sensitive troponin T (HsTnT),&#xD;
      Interleukin-6, Interleukin-18 and high sensitive C-reactive protein. Moreover, after 24 and&#xD;
      48 hours of admission, fasting blood glucose levels, hemoglobin, Lactate, Base Deficit,&#xD;
      Interleukin-6, Interleukin-18 and high sensitive C-reactive protein will be repeated for all&#xD;
      the patients. The main exposure will be hyperglycemia, defined as serum glucose 200 mg/dL or&#xD;
      more. This level of glucose has previously been used by several trauma studies, and it is a&#xD;
      commonly utilized cutoff to define hyperglycemia. Diabetes mellitus will be determined by&#xD;
      patient history and/or admission HbA1c ≥ 6.5%. This level of HbA1c is based on current&#xD;
      recommendations for the diagnosis of diabetes mellitus from the American Diabetes Association&#xD;
      [10]. All the study participants will be managed according to the standard care of the&#xD;
      hospital.&#xD;
&#xD;
      The investigators expect to enroll 250 consecutive trauma patients to be included in the&#xD;
      study from the Hamad General Hospital, Doha, Qatar (this number of participants will be per&#xD;
      center in case it becomes multicenter study to reach 750-1000 in total). The subject will be&#xD;
      in the research until discharge from the hospital or died in the hospital and there will be&#xD;
      no follow-up visits for the research.&#xD;
&#xD;
      Data collection &amp; integrity: For each study participant, information will be collected&#xD;
      regarding demographics (e.g., age, sex, nationality), injury (i.e., injury mechanism, ISS),&#xD;
      and clinical characteristics (i.e., hospital stay, ICU days, and days on ventilator support).&#xD;
      Information will be collected regarding outcomes, including mortality and in-hospital&#xD;
      complications (i.e., pneumonia, renal failure, sepsis, Acute Respiratory Distress Syndrome&#xD;
      and multiorgan failure).&#xD;
&#xD;
      The principal investigator (PI) will provide specific pre-assigned numbers to each sample&#xD;
      collected and only the PI will know the subject identifier and all others will work with the&#xD;
      number only. However, in the process of receiving and storage of samples, one appointed&#xD;
      technical staff of laboratory services can have the access to the blood specimens. The&#xD;
      investigator will track all the specimens received by allotting unique subject identifier for&#xD;
      all blood specimens and track the sample transportation, processing, and consumption. Each&#xD;
      sample will be labeled properly in color-coded cryo boxes at -80°C and will be discarded&#xD;
      immediately after the test. Only the PI will have the access to the data which has been coded&#xD;
      with subject identifier. The de-identified data from the individual data collection sheet&#xD;
      will be entered by the research coordinator into the password protected Excel file.&#xD;
&#xD;
      Participation in this study is voluntary and the participant can be discontinued at any time,&#xD;
      if he/she is willing to withdraw. If the participant is interested to withdraw from the&#xD;
      study, he/she needs to contact the lead principle investigators of the study and this&#xD;
      decision will not affect their medical care. In case of subjects recruited by emergency&#xD;
      consent, after patient recovery he/she will have the right to withdraw from the study at any&#xD;
      time voluntarily. If the patient chooses to withdraw from the study, they will be asked for&#xD;
      permission to use their data up to the time of withdrawal. Data will be collected up to the&#xD;
      time of withdrawal. Data will be collected up to the time of withdrawal. The existing data&#xD;
      will not be removed from research and will be used for intention-to-treat analysis. However,&#xD;
      the specimens will be discarded and no further data will be generated.&#xD;
&#xD;
      Data management: Data collection sheet will be used to record all relevant information of&#xD;
      individual subjects. The de-identified data from the individual data collection sheet will be&#xD;
      entered by the research coordinator into the password protected Excel file. Only the PI will&#xD;
      have the access to the data which has been coded with subject identifier. The PI designated&#xD;
      research team member will have the access to the de-identified data. Data will be stored and&#xD;
      secured at logbook/secured computer with the PI. Hard copies will also be stored in closed&#xD;
      envelopes in locked cabinets in PI's office. The data will be kept for a period of five years&#xD;
      and then later will be destroyed. Data will be stored by the Hamad Trauma Center (HTC) Lead&#xD;
      PI from all the participating centers and no data will be transferred from HTC to other&#xD;
      centers. This study is opened for collaborative centers to be a multicenter study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>All cause Mortality</measure>
    <time_frame>30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pneumonia</measure>
    <time_frame>30 days</time_frame>
    <description>ventilator acquired infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sepsis</measure>
    <time_frame>30 days</time_frame>
    <description>The new definitions published in Journal of American Medical Association (2016;315:801-810)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiorgan failure</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">300</enrollment>
  <condition>Trauma</condition>
  <condition>Stress Induced Hyperglycemia</condition>
  <condition>Diabetes Mellitus</condition>
  <eligibility>
    <study_pop>
      <textblock>
        All adult (≥18 years) trauma patients required hospital admission will be screened for&#xD;
        participation in this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All adult (≥18 years) male and female trauma patients consented for participation and&#xD;
             have been investigated for random plasma glucose level and HbA1C measured within 5&#xD;
             hours of hospital admission will be included in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who descend to participate or in whom random serum glucose level and HbA1C&#xD;
             not measured within 5 hours of hospital admission will be excluded from the study.&#xD;
&#xD;
          -  Also, vulnerable populations (children, and pregnant women), and alcoholics will be&#xD;
             excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ayman El-Menyar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hamad Medical Coorporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hamad Medical Coorporation</name>
      <address>
        <city>Doha</city>
        <zip>3050</zip>
        <country>Qatar</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Qatar</country>
  </location_countries>
  <reference>
    <citation>McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin. 2001 Jan;17(1):107-24. doi: 10.1016/s0749-0704(05)70154-8.</citation>
    <PMID>11219223</PMID>
  </reference>
  <reference>
    <citation>Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycemia as a prognostic indicator in trauma. J Trauma. 2003 Jul;55(1):33-8. doi: 10.1097/01.TA.0000074434.39928.72.</citation>
    <PMID>12855878</PMID>
  </reference>
  <reference>
    <citation>Laird AM, Miller PR, Kilgo PD, Meredith JW, Chang MC. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma. 2004 May;56(5):1058-62. doi: 10.1097/01.ta.0000123267.39011.9f.</citation>
    <PMID>15179246</PMID>
  </reference>
  <reference>
    <citation>Kerby JD, Griffin RL, MacLennan P, Rue LW 3rd. Stress-induced hyperglycemia, not diabetic hyperglycemia, is associated with higher mortality in trauma. Ann Surg. 2012 Sep;256(3):446-52. doi: 10.1097/SLA.0b013e3182654549.</citation>
    <PMID>22868366</PMID>
  </reference>
  <reference>
    <citation>Bosarge PL, Shoultz TH, Griffin RL, Kerby JD. Stress-induced hyperglycemia is associated with higher mortality in severe traumatic brain injury. J Trauma Acute Care Surg. 2015 Aug;79(2):289-94. doi: 10.1097/TA.0000000000000716.</citation>
    <PMID>26218699</PMID>
  </reference>
  <reference>
    <citation>Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery. 2000 Feb;46(2):335-42; discussion 342-3. doi: 10.1097/00006123-200002000-00015.</citation>
    <PMID>10690722</PMID>
  </reference>
  <reference>
    <citation>Wei Y, Chen K, Whaley-Connell AT, Stump CS, Ibdah JA, Sowers JR. Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R673-80. doi: 10.1152/ajpregu.00561.2007. Epub 2007 Dec 19.</citation>
    <PMID>18094066</PMID>
  </reference>
  <reference>
    <citation>Esposito K, Marfella R, Giugliano D. Plasma interleukin-18 concentrations are elevated in type 2 diabetes. Diabetes Care. 2004 Jan;27(1):272. doi: 10.2337/diacare.27.1.272. No abstract available.</citation>
    <PMID>14694002</PMID>
  </reference>
  <reference>
    <citation>Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet. 2009 May 23;373(9677):1798-807. doi: 10.1016/S0140-6736(09)60553-5.</citation>
    <PMID>19465235</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>July 22, 2020</last_update_submitted>
  <last_update_submitted_qc>July 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hamad Medical Corporation</investigator_affiliation>
    <investigator_full_name>Dr. Ayman El-Menyar</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>stress, hyperglycemia, inflammatory markers, trauma, HbA1c</keyword>
  <keyword>interleukin-6</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperglycemia</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Only the lead PI will have the access to the data which will be coded with subject identifier to ensure data safety and confidentiality. The study will be opened for collaboration with multi-centers. Data from other centers will be shared with the Lead PI.</ipd_description>
  </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/NCT02999386
org study id: 14471/14
nct id: NCT02999386
lead sponsor: 
has dmc: No
The clinical relevance of the observed stress induced hyperglycemia in trauma patients
      remains unclear. The earlier studies suggested the implications of cytokines in stress
      induced hyperglycemia and the outcomes after trauma. To date, there is little information
      available regarding the effect of diabetic hyperglycemia (occult or known) on outcomes after
      trauma and whether these patients represent a distinct group with differential outcomes when
      compared to those with stress-induced hyperglycemia. Herein, the purpose of this study is to
      identify the incidence of stress induced hyperglycemia as well as diabetic hyperglycemia in
      trauma patients and to investigate the association between proinflammatory cytokine levels
      and hyperglycemia in our trauma population.
Intensive glucose control is vital for prognosis and preservation of normal physiologic
      status in trauma patients. The acute effects of severe trauma, infection, and surgery result
      in remarkable metabolic stress on the human body. Hyperglycemia is a normal metabolic
      response to stress and injury [1]. Irrespective of the involved injury mechanism,
      post-traumatic metabolic changes occur due to stress in terms of an increased glucose
      production, decreased insulin production, and insulin resistance in the peripheral tissues
      and eventually lead to a state of hyperglycemia. Traumatic injury also induces changes in
      endogenous hormone production and enhanced utilization of metabolites that usually lead to
      stress related hyperglycemia. Measurement of HbA1c levels can be used as a screening tool to
      discriminate unknown diabetes mellitus from stress-induced hyperglycemia (SIH). Published
      studies that have evaluated the association between presenting hyperglycemia and worse
      outcomes in trauma patients have all consistently showed higher mortality and infection rates
      in patients presented with elevated serum glucose levels of 200 mg/dL or more [2-5]. A recent
      study evaluated the differential effect of SIH in comparison to diabetic hyperglycemia (DH)
      on outcomes in trauma victims. The authors observed that as opposed to DH, SIH is associated
      with a higher mortality rate after injury [4]. A prospective study of patients with severe
      traumatic brain injury demonstrated that admission glucose levels >11.1 mmol/L were
      associated with increased mortality and poor neurologic outcomes [6]. Stress associated with
      critical illness is characterized by the activation of inflammatory cellular mediators [7].
      During acute illness there is an increase in the systemic inflammatory response that is
      characterized by increased production of pro-inflammatory cytokines. Importantly, there is
      relationship between abnormal cytokine production and hyperglycemia in severe sepsis patients
      which aggravates the immune response leading to poor clinical outcomes. Recent studies
      suggested that interleukin-6 (IL-6) is involved in glucose metabolism and insulin action. The
      proinflammatory IL-6 is normally released upon infection; however, it induces insulin
      resistance during conditions of hyperglycemia [8]. Moreover, IL-18 levels are significantly
      elevated in diabetic patients with microalbuminuria as compared with patients with
      normoalbuminuria [9]. This might indicate that certain interleukins (IL) are involved in the
      pathogenesis of SIH. Though, the clinical relevance of the observed SIH in trauma patients
      remains unclear. The earlier studies suggested the implications of cytokines in SIH and
      outcomes after trauma. To date, there is little information regarding the effect of diabetic
      hyperglycemia (occult or known) on the clinical outcomes after trauma and whether these
      patients represent a distinct group with differential outcomes when compared to those with
      SIH. The purpose of this study is to identify the incidence of SIH as well as diabetic
      hyperglycemia in trauma patients and to investigate the association between the
      proinflammatory cytokine levels and hyperglycemia in trauma population.

      Primary objective:

      - To evaluate the outcomes of stress induced hyperglycemia in patients presented with
      traumatic injury.

      Secondary objectives:

        -  To investigate the association between pro-inflammatory cytokine levels and SIH in
           trauma patients.

        -  To identify the incidence of SIH and occult diabetes mellitus in trauma population.

      It is a prospective study which will include all adult trauma patients who require hospital
      admission and have been investigated for random plasma glucose level and HbA1C measured
      within 5 hours of admission. All trauma patients will undergo thorough clinical assessment
      and resuscitation according to the Advanced Trauma Life Support (ATLS) guidelines. The
      present study will screen all traumatic injury patients presented to the trauma room and
      those who are willing to participate and provide written informed consent or consented by the
      relatives or used emergency consent (Exception from Informed Consent Requirements for
      Emergency Research" Policy # 11026) to draw blood for the investigations will be included in
      the study. All the study subjects will be managed according to the standard care of the
      hospital. The investigators will directly access all adult traumatic injury patients that
      will be presented to the trauma room and review the medical file and/or electronic medical
      record (EMR) to confirm the eligibility. Usually trauma patients are unconscious, under shock
      and are physically and mentally unfit to communicate or sign consent. The trauma surgeon will
      explain the consent form to the legal representatives of the subjects in a separate chamber
      in the ICU or in private room in the clinic.

      Consent and recruitment procedures will be done in such a way that it will not be disclosed
      to other patients in the trauma room or in the ward. The information regarding patient's
      enrollment will be kept confidential and all study related interactions with the
      subject/patient's legal representative will be done in isolated room in the wards or in the
      clinics to maintain complete privacy. To safeguards the severe trauma patients, informed
      consent will be taken to participate in research by a legally authorized representative on
      behalf of a cognitively impaired subject. In absence of any legally authorized
      representative, the investigators will use emergency consent (Exception from Informed Consent
      Requirements for Emergency Research" Policy # 11026).

      Patients who partially recover cognition will be asked to provide Assent and those fully
      recovered their cognition to understand the study will be asked for informed consent to
      continue participation. For trauma patients who are unconscious, under severe shock and are
      physically and mentally unfit to communicate, legally authorized representative will be
      identified with the help of patient's attendants. Explaining the consent will take around
      half an hour, and if the legal representative consented to allow subject participation within
      5 hours of admission, he/she will be enrolled. Since the research investigations needs to be
      done during early hours of admission waiting time could be maximum 2-3 hours post admission.
      This study did not include any specific procedure which could provide distress to the
      participants. And the subject's privacy will be specifically taken care.

      Sample size estimation: There is lack of information on the incidence of stress-induced
      hyperglycemia among trauma patients in Qatar. However, the current literature reported the
      incidence of stress-induced hyperglycemia (≥200 mg/dl) in trauma patients ranges from 10%-17%
      for all trauma admissions [3,4]. Therefore, taking the frequency of hyperglycemia to be 15%
      with 5% confidence limit and 97% confidence level, a total of 250 consecutive trauma patients
      needs to be included in the study. The investigators aim to complete the target of subject
      recruitment within 12 months and this research may take 18 months to be completed.

      Bio-specimens: The blood specimen for research (10 ml initially after recruitment and 5 ml
      after 24 and 48 hours of admission) will be drawn together with the routine blood
      investigation.

      For each study participant, blood will be drawn on admission to investigate Hemoglobin,
      HbA1C, blood glucose levels, Lactate, Base Deficit, High sensitive troponin T (HsTnT),
      Interleukin-6, Interleukin-18 and high sensitive C-reactive protein. Moreover, after 24 and
      48 hours of admission, fasting blood glucose levels, hemoglobin, Lactate, Base Deficit,
      Interleukin-6, Interleukin-18 and high sensitive C-reactive protein will be repeated for all
      the patients. The main exposure will be hyperglycemia, defined as serum glucose 200 mg/dL or
      more. This level of glucose has previously been used by several trauma studies, and it is a
      commonly utilized cutoff to define hyperglycemia. Diabetes mellitus will be determined by
      patient history and/or admission HbA1c ≥ 6.5%. This level of HbA1c is based on current
      recommendations for the diagnosis of diabetes mellitus from the American Diabetes Association
      [10]. All the study participants will be managed according to the standard care of the
      hospital.

      The investigators expect to enroll 250 consecutive trauma patients to be included in the
      study from the Hamad General Hospital, Doha, Qatar (this number of participants will be per
      center in case it becomes multicenter study to reach 750-1000 in total). The subject will be
      in the research until discharge from the hospital or died in the hospital and there will be
      no follow-up visits for the research.

      Data collection & integrity: For each study participant, information will be collected
      regarding demographics (e.g., age, sex, nationality), injury (i.e., injury mechanism, ISS),
      and clinical characteristics (i.e., hospital stay, ICU days, and days on ventilator support).
      Information will be collected regarding outcomes, including mortality and in-hospital
      complications (i.e., pneumonia, renal failure, sepsis, Acute Respiratory Distress Syndrome
      and multiorgan failure).

      The principal investigator (PI) will provide specific pre-assigned numbers to each sample
      collected and only the PI will know the subject identifier and all others will work with the
      number only. However, in the process of receiving and storage of samples, one appointed
      technical staff of laboratory services can have the access to the blood specimens. The
      investigator will track all the specimens received by allotting unique subject identifier for
      all blood specimens and track the sample transportation, processing, and consumption. Each
      sample will be labeled properly in color-coded cryo boxes at -80°C and will be discarded
      immediately after the test. Only the PI will have the access to the data which has been coded
      with subject identifier. The de-identified data from the individual data collection sheet
      will be entered by the research coordinator into the password protected Excel file.

      Participation in this study is voluntary and the participant can be discontinued at any time,
      if he/she is willing to withdraw. If the participant is interested to withdraw from the
      study, he/she needs to contact the lead principle investigators of the study and this
      decision will not affect their medical care. In case of subjects recruited by emergency
      consent, after patient recovery he/she will have the right to withdraw from the study at any
      time voluntarily. If the patient chooses to withdraw from the study, they will be asked for
      permission to use their data up to the time of withdrawal. Data will be collected up to the
      time of withdrawal. Data will be collected up to the time of withdrawal. The existing data
      will not be removed from research and will be used for intention-to-treat analysis. However,
      the specimens will be discarded and no further data will be generated.

      Data management: Data collection sheet will be used to record all relevant information of
      individual subjects. The de-identified data from the individual data collection sheet will be
      entered by the research coordinator into the password protected Excel file. Only the PI will
      have the access to the data which has been coded with subject identifier. The PI designated
      research team member will have the access to the de-identified data. Data will be stored and
      secured at logbook/secured computer with the PI. Hard copies will also be stored in closed
      envelopes in locked cabinets in PI's office. The data will be kept for a period of five years
      and then later will be destroyed. Data will be stored by the Hamad Trauma Center (HTC) Lead
      PI from all the participating centers and no data will be transferred from HTC to other
      centers. This study is opened for collaborative centers to be a multicenter study.
observational model: Cohort
time perspective: Prospective
measure: All cause Mortality
time frame: 30 days
measure: Pneumonia
time frame: 30 days
description: ventilator acquired infection
measure: Sepsis
time frame: 30 days
description: The new definitions published in Journal of American Medical Association (2016;315:801-810)
measure: Multiorgan failure
time frame: 30 days
measure: Hospital length of stay
time frame: 1 year
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Ayman El-Menyar, MD
role: Principal Investigator
affiliation: Hamad Medical Coorporation
facility: 
country: Qatar
citation: McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin. 2001 Jan;17(1):107-24. doi: 10.1016/s0749-0704(05)70154-8.
PMID: 11219223
citation: Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycemia as a prognostic indicator in trauma. J Trauma. 2003 Jul;55(1):33-8. doi: 10.1097/01.TA.0000074434.39928.72.
PMID: 12855878
citation: Laird AM, Miller PR, Kilgo PD, Meredith JW, Chang MC. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma. 2004 May;56(5):1058-62. doi: 10.1097/01.ta.0000123267.39011.9f.
PMID: 15179246
citation: Kerby JD, Griffin RL, MacLennan P, Rue LW 3rd. Stress-induced hyperglycemia, not diabetic hyperglycemia, is associated with higher mortality in trauma. Ann Surg. 2012 Sep;256(3):446-52. doi: 10.1097/SLA.0b013e3182654549.
PMID: 22868366
citation: Bosarge PL, Shoultz TH, Griffin RL, Kerby JD. Stress-induced hyperglycemia is associated with higher mortality in severe traumatic brain injury. J Trauma Acute Care Surg. 2015 Aug;79(2):289-94. doi: 10.1097/TA.0000000000000716.
PMID: 26218699
citation: Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery. 2000 Feb;46(2):335-42; discussion 342-3. doi: 10.1097/00006123-200002000-00015.
PMID: 10690722
citation: Wei Y, Chen K, Whaley-Connell AT, Stump CS, Ibdah JA, Sowers JR. Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R673-80. doi: 10.1152/ajpregu.00561.2007. Epub 2007 Dec 19.
PMID: 18094066
citation: Esposito K, Marfella R, Giugliano D. Plasma interleukin-18 concentrations are elevated in type 2 diabetes. Diabetes Care. 2004 Jan;27(1):272. doi: 10.2337/diacare.27.1.272. No abstract available.
PMID: 14694002
citation: Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet. 2009 May 23;373(9677):1798-807. doi: 10.1016/S0140-6736(09)60553-5.
PMID: 19465235
responsible party type: Principal Investigator
investigator affiliation: Hamad Medical Corporation
investigator full name: Dr. Ayman El-Menyar
investigator title: Associate Professor
mesh term: Hyperglycemia
mesh term: Wounds and Injuries
sharing ipd: No
ipd description: Only the lead PI will have the access to the data which will be coded with subject identifier to ensure data safety and confidentiality. The study will be opened for collaboration with multi-centers. Data from other centers will be shared with the Lead PI.