<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/NCT03280485</url>
  </required_header>
  <id_info>
    <org_study_id>no number</org_study_id>
    <nct_id>NCT03280485</nct_id>
  </id_info>
  <brief_title>Validation of the Scandinavian Guidelines for Management of TBI in Adults</brief_title>
  <official_title>Multicenter Validation of the Scandinavian Guidelines for Management of Minimal, Mild and Moderate Head Injury in Adults: a Study Protocol.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Halmstad County Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Halmstad County Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      Traumatic brain injuries (TBI) are one of the most common reasons for patients to attend the&#xD;
      emergency department (ED). 90% of patients with TBI are defined as mild TBI (mTBI).&#xD;
&#xD;
      A small minority of patients with mTBI would show pathological computed tomography (CT)&#xD;
      results and even fewer need neurosurgical intervention. Nevertheless, complications would be&#xD;
      so severe, if neurosurgical intervention is delayed, that it has become common practice to&#xD;
      subject all patients with mTBI to CT. The high number of CT scans has an impact on health&#xD;
      care resources but may also involve risk by subjecting patients through potentially harmful&#xD;
      ionizing radiation.&#xD;
&#xD;
      Several independent research groups have attempted to optimize CT use in mTBI patients by&#xD;
      forming guidelines that aim to identify patients at high risk for intracranial complications.&#xD;
      Most guidelines have been published in the past 15 years and have been validated both&#xD;
      prospectively internally and externally; all guidelines have been shown to be safe when&#xD;
      implemented in clinical use with few missed complications. However the number of CT scans has&#xD;
      not been reduced dramatically, in some cases it has even increased.&#xD;
&#xD;
      In 2013, the new Scandinavian guidelines (SNC13) were published. They are the first&#xD;
      guidelines that use a biomarker, S100B, as a tool for managing patients with mTBI. Although&#xD;
      S100B has a low specificity for intracranial complications, a high sensitivity makes it&#xD;
      suitable to be implemented into clinical practice as a tool for CT reduction. Previous SNC&#xD;
      guidelines have been compared to other prominent guidelines with impressive results. The&#xD;
      SNC13 have been externally validated in a retrospective study from the USA that was&#xD;
      underpowered for important outcomes. Nevertheless, SNC13 have already been partially&#xD;
      implemented in clinical practice in Scandinavia. However, a strict multicenter validation has&#xD;
      not been performed yet nor a systematic comparison to other available guidelines.&#xD;
&#xD;
      Our primary aim is to validate the performance of the SNC13 in predicting intracranial&#xD;
      complications in adult patients presenting with traumatic head injury in Swedish hospitals. A&#xD;
      secondary aim is to compare the performance of SNC 13 with 6 other clinical guidelines, with&#xD;
      respect to important outcomes. Moreover, to explore the performances of different biomarkers&#xD;
      in predicting intracranial complications in predefined subgroups of TBI. Finally, to evaluate&#xD;
      the possibility of further improvement of the SNC13.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design Investigators will perform a prospective, multicenter, pragmatic, observational study&#xD;
      of adults presenting with traumatic head injury at the ED.&#xD;
&#xD;
      All data necessary for analysis including predictor variables and outcome data for all the&#xD;
      seven guidelines included in the study will be registered (table 1). Patients will be managed&#xD;
      clinically accordingly to the judgment of the responsible physician and/or local guidelines.&#xD;
&#xD;
      Study setting and population The study will be set in Halmstad, Malmö, Lund, Örebro and&#xD;
      Linköping, Sweden. Hallands Hospital Halmstad (HS) is a level II trauma centre, Skåne&#xD;
      University Hospital in Malmö and Lund (SUS), Örebro University Hospital, Linköping University&#xD;
      Hospital are level I trauma centers.&#xD;
&#xD;
      The coordinating site for the study will be HS where the statistical and the comparative&#xD;
      biomarker analysis will be performed.&#xD;
&#xD;
      Inclusion criteria From September 2017 investigators will prospectively enroll all adult&#xD;
      patients with a GCS 9-15 that seek the ED within 24h after TBI.&#xD;
&#xD;
      Exclusion criteria&#xD;
&#xD;
        -  patients younger than 18 years of age;&#xD;
&#xD;
        -  patients without a Swedish personal identification number due to difficulties in&#xD;
           performing the follow up phase;&#xD;
&#xD;
        -  all patients that refuse to participate.&#xD;
&#xD;
      Data registration and follow-up Details of how patients are managed, including patient&#xD;
      characteristics, injury type, patient history, clinical examination results, current&#xD;
      medications and CT findings will be documented in a pre-determined case-report form by the&#xD;
      triage nurse and/or physician on call.&#xD;
&#xD;
      All patients will be asked to answer a questionnaire sent by mail 3 months after the injury.&#xD;
      The questionnaire will be re-sent if no answer is received. If no answer is received from&#xD;
      these attempts, patients will be contacted via telephone. The questionnaire includes&#xD;
      questions that would identify a significant intracranial lesion, data concerning sick-days,&#xD;
      new contacts with medical professionals and information concerning quality of life. In cases&#xD;
      where patients can not be reached by mail or telephone, medical records and national&#xD;
      mortality databases will be consulted for evidence of complications and/or death. The Swedish&#xD;
      health care system allows full visibility of data for persons with a Swedish personal&#xD;
      identification number for medical records and mortality database over the whole country.&#xD;
      Patients who suffer significant (enough to seek medical care) intracranial complications&#xD;
      after discharge would therefore be identified.&#xD;
&#xD;
      Details on study period are specified on figure 1 with an algorithm for patient eligibility&#xD;
      and data analysis.&#xD;
&#xD;
      Data will be registered in an Excel® file. Descriptive statistics will be analysed using IBM&#xD;
      SPSS® Statistics Version 20 software.&#xD;
&#xD;
      S100B analysis A 5ml blood sample is drawn from patient's cubital vein in the ED. Samples are&#xD;
      analysed with the fully automated Elecsys® S100 (Roche AB) at the Clinical Chemistry&#xD;
      Department of HS, SUS, Örebro University Hospital and Linköping University Hospital, Sweden.&#xD;
      Cut-off level for normal levels of S100B according to the SNC guidelines is less than&#xD;
      0.10μg/L and a window of sampling of within 6 hours from the time of the injury.&#xD;
&#xD;
      From all patients seeking care within 24h form injury with medium and low risk TBI, according&#xD;
      to SNC13 (including multitrauma patients), a 5ml blood sample will be drawn, centrifuged and&#xD;
      frozen at -70 degrees Celsius. Samplings will be coded and registered for analysis of GFAP,&#xD;
      SBP-50 and TAU.&#xD;
&#xD;
      CT examinations CT scans are always analysed by a board certified radiologist.&#xD;
&#xD;
      Sample size The Scandinavian guidelines will recommend discharge (i.e. neither CT nor&#xD;
      admission) in approximately 50% of patients and a prevalence of our primary outcome of 5%&#xD;
      (from our own observations and from data derived from a pre-selected cohort) . Allowing for&#xD;
      one missed case, a sensitivity of &gt;99% with a lower 95% confidence interval, a sample size of&#xD;
      2490 patients is required to detect traumatic intracranial complications according to the&#xD;
      SNC13. Allowing for a 10% lost to follow-up, the desired sample size is 2767 patients.&#xD;
&#xD;
      Interim analysis After 1000 patients, the prevalence for the primary outcome will be measured&#xD;
      in order to be able to reevaluate sample size.&#xD;
&#xD;
      Ethics Ethical approval was granted from the Regional Ethical Review Board of Lund (approval&#xD;
      number 2012/574).&#xD;
&#xD;
      Informed verbal consent will be obtained and registered by nurses responsible for triage at&#xD;
      ED.&#xD;
&#xD;
      Patients' data and social security number will be stored and handled accordingly to Swedish&#xD;
      Personal Data Act, (PUL 1998: 204).&#xD;
&#xD;
      Written consent will be obtained from all patients from whom the extra blood sampling for&#xD;
      biomarker analysis will be requested. Sampling will be coded and patients will be able at any&#xD;
      time to refuse to be part of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 10, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>3 Months</target_duration>
  <primary_outcome>
    <measure>Neurosurgery</measure>
    <time_frame>4 years</time_frame>
    <description>Need for any neurosurgical proceedure or intervention within 1 week of injury</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intracranial complication</measure>
    <time_frame>4 years</time_frame>
    <description>composite variable of death as consequence of the TBI, need for neurosurgical intervention or marked abnormality on CT</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>serious CT findings</measure>
    <time_frame>4 years</time_frame>
    <description>contusions larger than 5mm in diameter, subarachnoid bleeding thicker than 1mm, subdural hematoma thicker than 4mm, pneumocephaly that will need intervention, depressed skull fracture through the inner table.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CT findings</measure>
    <time_frame>4 years</time_frame>
    <description>Any pathological traumatic CT finding</description>
  </secondary_outcome>
  <enrollment type="Anticipated">3000</enrollment>
  <condition>Traumatic Brain Injury</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>no intervention</intervention_name>
    <description>no intervention validation of guidelines via database</description>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      A 5ml blood sample is drawn from patient's cubital vein in the ED. Samples are analysed with&#xD;
      the fully automated Elecsys® S100 (Roche AB) at the Clinical Chemistry Department of HS, SUS,&#xD;
      Örebro University Hospital and Linköping University Hospital, Sweden. Cut-off level for&#xD;
      normal levels of S100B according to the SNC guidelines is less than 0.10μg/L and a window of&#xD;
      sampling of within 6 hours from the time of the injury.&#xD;
&#xD;
      From all patients seeking care within 24h form injury with medium and low risk TBI, according&#xD;
      to SNC13 (including multitrauma patients), a 5ml blood sample will be drawn, centrifuged and&#xD;
      frozen at -70 degrees Celsius. Samplings will be coded and registered for analysis of GFAP,&#xD;
      SBP-50 and TAU.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        adults with TBI&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  From September 2017 we will prospectively enroll all adult patients with a GCS 9-15&#xD;
             that seek the ED in Halmstad, Malmo, Lund, Linkoping, Orebro (Sweden) within 24h after&#xD;
             TBI.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
        We will exclude:&#xD;
&#xD;
          -  patients younger than 18 years of age;&#xD;
&#xD;
          -  patients without a Swedish personal identification number due to difficulties in&#xD;
             performing the follow up phase;&#xD;
&#xD;
          -  all patients that refuse to participate.&#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>Olga Calcagnile, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Halland Hospital Halmstad</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Olga Calcagnile, MD, PhD</last_name>
    <phone>004635131000</phone>
    <email>olga.calcagnile@regionhalland.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Johan Undén, PhD, MD</last_name>
    <phone>004635131000</phone>
    <email>johan.unden@regionhalland.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Halland Hospital Halmstad</name>
      <address>
        <city>Halmstad</city>
        <zip>302 64</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olga Calcagnile, MD, PhD</last_name>
      <phone>035-131000</phone>
      <email>olga.calcagnile@regionhalland.se</email>
    </contact>
    <contact_backup>
      <last_name>Johan Undén, PhD, MD</last_name>
      <phone>035-131000</phone>
      <email>johan.unden@regionhalland.se</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>September 21, 2017</last_update_submitted>
  <last_update_submitted_qc>September 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Halmstad County Hospital</investigator_affiliation>
    <investigator_full_name>Olga Calcagnile</investigator_full_name>
    <investigator_title>Medical doctor, PhD</investigator_title>
  </responsible_party>
  <keyword>TBI</keyword>
  <keyword>management</keyword>
  <keyword>S100B</keyword>
  <keyword>biomarkers</keyword>
  <keyword>mild head injury</keyword>
  <keyword>intracranial complication</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 30, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT03280485/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03280485
org study id: no number
nct id: NCT03280485
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Traumatic brain injuries (TBI) are one of the most common reasons for patients to attend the
      emergency department (ED). 90% of patients with TBI are defined as mild TBI (mTBI).

      A small minority of patients with mTBI would show pathological computed tomography (CT)
      results and even fewer need neurosurgical intervention. Nevertheless, complications would be
      so severe, if neurosurgical intervention is delayed, that it has become common practice to
      subject all patients with mTBI to CT. The high number of CT scans has an impact on health
      care resources but may also involve risk by subjecting patients through potentially harmful
      ionizing radiation.

      Several independent research groups have attempted to optimize CT use in mTBI patients by
      forming guidelines that aim to identify patients at high risk for intracranial complications.
      Most guidelines have been published in the past 15 years and have been validated both
      prospectively internally and externally; all guidelines have been shown to be safe when
      implemented in clinical use with few missed complications. However the number of CT scans has
      not been reduced dramatically, in some cases it has even increased.

      In 2013, the new Scandinavian guidelines (SNC13) were published. They are the first
      guidelines that use a biomarker, S100B, as a tool for managing patients with mTBI. Although
      S100B has a low specificity for intracranial complications, a high sensitivity makes it
      suitable to be implemented into clinical practice as a tool for CT reduction. Previous SNC
      guidelines have been compared to other prominent guidelines with impressive results. The
      SNC13 have been externally validated in a retrospective study from the USA that was
      underpowered for important outcomes. Nevertheless, SNC13 have already been partially
      implemented in clinical practice in Scandinavia. However, a strict multicenter validation has
      not been performed yet nor a systematic comparison to other available guidelines.

      Our primary aim is to validate the performance of the SNC13 in predicting intracranial
      complications in adult patients presenting with traumatic head injury in Swedish hospitals. A
      secondary aim is to compare the performance of SNC 13 with 6 other clinical guidelines, with
      respect to important outcomes. Moreover, to explore the performances of different biomarkers
      in predicting intracranial complications in predefined subgroups of TBI. Finally, to evaluate
      the possibility of further improvement of the SNC13.
Design Investigators will perform a prospective, multicenter, pragmatic, observational study
      of adults presenting with traumatic head injury at the ED.

      All data necessary for analysis including predictor variables and outcome data for all the
      seven guidelines included in the study will be registered (table 1). Patients will be managed
      clinically accordingly to the judgment of the responsible physician and/or local guidelines.

      Study setting and population The study will be set in Halmstad, Malmö, Lund, Örebro and
      Linköping, Sweden. Hallands Hospital Halmstad (HS) is a level II trauma centre, Skåne
      University Hospital in Malmö and Lund (SUS), Örebro University Hospital, Linköping University
      Hospital are level I trauma centers.

      The coordinating site for the study will be HS where the statistical and the comparative
      biomarker analysis will be performed.

      Inclusion criteria From September 2017 investigators will prospectively enroll all adult
      patients with a GCS 9-15 that seek the ED within 24h after TBI.

      Exclusion criteria

        -  patients younger than 18 years of age;

        -  patients without a Swedish personal identification number due to difficulties in
           performing the follow up phase;

        -  all patients that refuse to participate.

      Data registration and follow-up Details of how patients are managed, including patient
      characteristics, injury type, patient history, clinical examination results, current
      medications and CT findings will be documented in a pre-determined case-report form by the
      triage nurse and/or physician on call.

      All patients will be asked to answer a questionnaire sent by mail 3 months after the injury.
      The questionnaire will be re-sent if no answer is received. If no answer is received from
      these attempts, patients will be contacted via telephone. The questionnaire includes
      questions that would identify a significant intracranial lesion, data concerning sick-days,
      new contacts with medical professionals and information concerning quality of life. In cases
      where patients can not be reached by mail or telephone, medical records and national
      mortality databases will be consulted for evidence of complications and/or death. The Swedish
      health care system allows full visibility of data for persons with a Swedish personal
      identification number for medical records and mortality database over the whole country.
      Patients who suffer significant (enough to seek medical care) intracranial complications
      after discharge would therefore be identified.

      Details on study period are specified on figure 1 with an algorithm for patient eligibility
      and data analysis.

      Data will be registered in an Excel® file. Descriptive statistics will be analysed using IBM
      SPSS® Statistics Version 20 software.

      S100B analysis A 5ml blood sample is drawn from patient's cubital vein in the ED. Samples are
      analysed with the fully automated Elecsys® S100 (Roche AB) at the Clinical Chemistry
      Department of HS, SUS, Örebro University Hospital and Linköping University Hospital, Sweden.
      Cut-off level for normal levels of S100B according to the SNC guidelines is less than
      0.10μg/L and a window of sampling of within 6 hours from the time of the injury.

      From all patients seeking care within 24h form injury with medium and low risk TBI, according
      to SNC13 (including multitrauma patients), a 5ml blood sample will be drawn, centrifuged and
      frozen at -70 degrees Celsius. Samplings will be coded and registered for analysis of GFAP,
      SBP-50 and TAU.

      CT examinations CT scans are always analysed by a board certified radiologist.

      Sample size The Scandinavian guidelines will recommend discharge (i.e. neither CT nor
      admission) in approximately 50% of patients and a prevalence of our primary outcome of 5%
      (from our own observations and from data derived from a pre-selected cohort) . Allowing for
      one missed case, a sensitivity of >99% with a lower 95% confidence interval, a sample size of
      2490 patients is required to detect traumatic intracranial complications according to the
      SNC13. Allowing for a 10% lost to follow-up, the desired sample size is 2767 patients.

      Interim analysis After 1000 patients, the prevalence for the primary outcome will be measured
      in order to be able to reevaluate sample size.

      Ethics Ethical approval was granted from the Regional Ethical Review Board of Lund (approval
      number 2012/574).

      Informed verbal consent will be obtained and registered by nurses responsible for triage at
      ED.

      Patients' data and social security number will be stored and handled accordingly to Swedish
      Personal Data Act, (PUL 1998: 204).

      Written consent will be obtained from all patients from whom the extra blood sampling for
      biomarker analysis will be requested. Sampling will be coded and patients will be able at any
      time to refuse to be part of the study.
observational model: Cohort
time perspective: Prospective
measure: Neurosurgery
time frame: 4 years
description: Need for any neurosurgical proceedure or intervention within 1 week of injury
measure: Intracranial complication
time frame: 4 years
description: composite variable of death as consequence of the TBI, need for neurosurgical intervention or marked abnormality on CT
measure: serious CT findings
time frame: 4 years
description: contusions larger than 5mm in diameter, subarachnoid bleeding thicker than 1mm, subdural hematoma thicker than 4mm, pneumocephaly that will need intervention, depressed skull fracture through the inner table.
measure: CT findings
time frame: 4 years
description: Any pathological traumatic CT finding
intervention type: Other
intervention name: no intervention
description: no intervention validation of guidelines via database
A 5ml blood sample is drawn from patient's cubital vein in the ED. Samples are analysed with
      the fully automated Elecsys® S100 (Roche AB) at the Clinical Chemistry Department of HS, SUS,
      Örebro University Hospital and Linköping University Hospital, Sweden. Cut-off level for
      normal levels of S100B according to the SNC guidelines is less than 0.10μg/L and a window of
      sampling of within 6 hours from the time of the injury.

      From all patients seeking care within 24h form injury with medium and low risk TBI, according
      to SNC13 (including multitrauma patients), a 5ml blood sample will be drawn, centrifuged and
      frozen at -70 degrees Celsius. Samplings will be coded and registered for analysis of GFAP,
      SBP-50 and TAU.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Olga Calcagnile, MD, PhD
role: Principal Investigator
affiliation: Halland Hospital Halmstad
last name: Olga Calcagnile, MD, PhD
phone: 004635131000
email: olga.calcagnile@regionhalland.se
last name: Johan Undén, PhD, MD
phone: 004635131000
email: johan.unden@regionhalland.se
facility: 
status: Recruiting
contact: 
contact backup: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Halmstad County Hospital
investigator full name: Olga Calcagnile
investigator title: Medical doctor, PhD
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
sharing ipd: No
provided document: 