<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/NCT04500197</url>
  </required_header>
  <id_info>
    <org_study_id>L2015126</org_study_id>
    <nct_id>NCT04500197</nct_id>
  </id_info>
  <brief_title>A Study of MIcrocirculatory Perfusion Alterations in Severe Burn Injury</brief_title>
  <acronym>MIPA</acronym>
  <official_title>A Single-centre Prospective Observational Study of MIcrocirculatory Perfusion Alterations in Severe Burn Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maasstad Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maasstad Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective of our study is to focus on the efficiency of standard fluid resuscitation&#xD;
      in promoting tissue perfusion in severe burns patients (&gt;15% TBSA). The incidence of&#xD;
      microcirculatory perfusion alterations, according to a predefined arbitrary cut off value, in&#xD;
      patients with severe burns injury (&gt;15%TBSA) will be assessed during standard resuscitation&#xD;
      in the first 24 hours.&#xD;
&#xD;
      Secondary objectives are to assess differences in microcirculatory perfusion alterations&#xD;
      between early (&lt;12 hours post burn injury) and late standard resuscitation (&gt;12 hours post&#xD;
      burn injury) with addition of albumin to the regime.&#xD;
&#xD;
      And to measure several biomarkers of glycocalyx shedding, oxidative stress and inflammation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: There are valid concerns that resuscitation in burns shock is inadequate. A&#xD;
      tendency to over resuscitate patients seem to exist. Current guidelines were developed 35&#xD;
      years ago and clinical burn resuscitation has not advanced significantly, despite ongoing&#xD;
      research. The main goal of resuscitation is achieving organ perfusion and tissue oxygenation.&#xD;
      Inadequate fluid resuscitation of severe acute burns may result in hypovolemic shock and&#xD;
      death. Excessive fluid resuscitation may result in fluid overload, lung edema,&#xD;
      intra-abdominal hypertension, abdominal compartment syndrome and burn depth conversion with&#xD;
      increased requirement for escharotomies, fasciotomies and skin grafting. Monitoring of&#xD;
      adequacy of resuscitation in burns patients has always been guided by systemic hemodynamic&#xD;
      variables (macro circulation) like blood pressure, heart rate, stroke volume and urinary&#xD;
      output, being urine output the major indicator of successful resuscitation. Whether these end&#xD;
      points are successful in achieving adequate perfusion and oxygen transport to the tissues is&#xD;
      unknown and relies on the assumption that there is a hemodynamic coherence between the macro&#xD;
      and microcirculation whereby improving the macro circulation causes a parallel improvement in&#xD;
      the microcirculation Objective: The main objective of our study is to focus on the efficacy&#xD;
      of standard fluid resuscitation in promoting tissue perfusion.&#xD;
&#xD;
      Study design: Single-center, prospective, observational clinical study in the Maasstad&#xD;
      Hospital.&#xD;
&#xD;
      Study population: All adult patients who are admitted to the Intensive Care Unit with severe&#xD;
      burns over 15%TBSA and resuscitated with the standard resuscitation protocol will be&#xD;
      included.&#xD;
&#xD;
      Main study parameters/endpoints: Measurement of sublingual microcirculation with vessel&#xD;
      density and flow parameters. Also skin perfusion maps (Laser Speckle Imaging) will be&#xD;
      recorded. Blood and urine samples will also be used for measuring glycocalyx shedding&#xD;
      products.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness:&#xD;
&#xD;
      Microcirculation assessment and laser speckle imaging are non-invasive procedures, and there&#xD;
      are negligible risks. Blood tests will be used for measuring glycocalyx shedding products,&#xD;
      this is an invasive procedure which may increase the risk of contamination, patient&#xD;
      discomfort and in some extreme cases blood sample collection may be a burden on patient&#xD;
      haemoglobin levels which is prone to decrease in critical patients. Assessment is essential&#xD;
      for determining whether action is required to change our existing resuscitation regime for&#xD;
      critically ill burned patients. If the results show that the current resuscitation regime is&#xD;
      suboptimal, then motivation for changing the existing practice can lead to improved clinical&#xD;
      care and a reduction in over- or under resuscitation in the ICU environment with its&#xD;
      potential harmful effects.&#xD;
&#xD;
      The risks associated with participation can be considered negligible and the burden can be&#xD;
      considered minimal in this observational study. The patients taking part in this study will&#xD;
      have no direct benefit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 12, 2018</start_date>
  <completion_date type="Actual">September 15, 2020</completion_date>
  <primary_completion_date type="Actual">September 15, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of microcirculatory perfusion alterations in severe burns patients during standard fluid resuscitation.</measure>
    <time_frame>Changes in perfusion parameters will be measured on admission (time zero, T=0), four hours after admission (T=4), eight hours after admission (T=8), twelve hours after admission (T=12) and twenty-four hours after admission (T=24</time_frame>
    <description>The main objective of our study is to measure standard microcirculatory perfusion parameters during standard resuscitation at different time points after a severe burn injury. These perfusion parameters are total vessel density (TVD), proportion of perfused vessels (PPV), functional capillary density (FCD) and focus depth.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Microcirculatory perfusion alterations after administration of albumin.</measure>
    <time_frame>Changes in microcirculatory perfusion parameters will be measured directly after administration of albumin. This will be 12 hours after starting fluid resuscitation.</time_frame>
    <description>Secondary objectives are to measure changes in standard microcirculatory parameters before and after administration of albumin. Albumin will be administered 12 hours after admission of the patient.</description>
  </secondary_outcome>
  <enrollment type="Actual">21</enrollment>
  <condition>Microcirculation</condition>
  <condition>Burns</condition>
  <condition>Resuscitation</condition>
  <eligibility>
    <study_pop>
      <textblock>
        30 patients admitted to the ICU with a severe burn ≥15% TBSA will be given standard&#xD;
        resuscitation care and will be included&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ICU admission with a severe burn injuries of ≥15% TBSA&#xD;
&#xD;
          2. ≥ 18 years of age&#xD;
&#xD;
          3. Receiving standard resuscitation protocol for severe burn injury&#xD;
&#xD;
          4. Post burn time up to a maximum of 24 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Informed consent not obtained&#xD;
&#xD;
          2. (suspected) generalised infection&#xD;
&#xD;
          3. Other traumatic injury, which is supposed to generate a systemic inflammatory response&#xD;
             eg severe fractures, or other types of shock as a result of massive bleeding&#xD;
&#xD;
          4. Patients unlikely to survive &gt;24 hours&#xD;
&#xD;
          5. Decision not to initiate treatment&#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>Can Ince, Prof</last_name>
    <role>Study Director</role>
    <affiliation>Erasmus Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maasstad Hospital</name>
      <address>
        <city>Rotterdam</city>
        <state>Zuid Nederland</state>
        <zip>3079DZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 20, 2019</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>October 13, 2020</last_update_submitted>
  <last_update_submitted_qc>October 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>microcirculation</keyword>
  <keyword>burns</keyword>
  <keyword>resuscitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burns</mesh_term>
  </condition_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/NCT04500197
org study id: L2015126
nct id: NCT04500197
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The main objective of our study is to focus on the efficiency of standard fluid resuscitation
      in promoting tissue perfusion in severe burns patients (>15% TBSA). The incidence of
      microcirculatory perfusion alterations, according to a predefined arbitrary cut off value, in
      patients with severe burns injury (>15%TBSA) will be assessed during standard resuscitation
      in the first 24 hours.

      Secondary objectives are to assess differences in microcirculatory perfusion alterations
      between early (<12 hours post burn injury) and late standard resuscitation (>12 hours post
      burn injury) with addition of albumin to the regime.

      And to measure several biomarkers of glycocalyx shedding, oxidative stress and inflammation.
Rationale: There are valid concerns that resuscitation in burns shock is inadequate. A
      tendency to over resuscitate patients seem to exist. Current guidelines were developed 35
      years ago and clinical burn resuscitation has not advanced significantly, despite ongoing
      research. The main goal of resuscitation is achieving organ perfusion and tissue oxygenation.
      Inadequate fluid resuscitation of severe acute burns may result in hypovolemic shock and
      death. Excessive fluid resuscitation may result in fluid overload, lung edema,
      intra-abdominal hypertension, abdominal compartment syndrome and burn depth conversion with
      increased requirement for escharotomies, fasciotomies and skin grafting. Monitoring of
      adequacy of resuscitation in burns patients has always been guided by systemic hemodynamic
      variables (macro circulation) like blood pressure, heart rate, stroke volume and urinary
      output, being urine output the major indicator of successful resuscitation. Whether these end
      points are successful in achieving adequate perfusion and oxygen transport to the tissues is
      unknown and relies on the assumption that there is a hemodynamic coherence between the macro
      and microcirculation whereby improving the macro circulation causes a parallel improvement in
      the microcirculation Objective: The main objective of our study is to focus on the efficacy
      of standard fluid resuscitation in promoting tissue perfusion.

      Study design: Single-center, prospective, observational clinical study in the Maasstad
      Hospital.

      Study population: All adult patients who are admitted to the Intensive Care Unit with severe
      burns over 15%TBSA and resuscitated with the standard resuscitation protocol will be
      included.

      Main study parameters/endpoints: Measurement of sublingual microcirculation with vessel
      density and flow parameters. Also skin perfusion maps (Laser Speckle Imaging) will be
      recorded. Blood and urine samples will also be used for measuring glycocalyx shedding
      products.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness:

      Microcirculation assessment and laser speckle imaging are non-invasive procedures, and there
      are negligible risks. Blood tests will be used for measuring glycocalyx shedding products,
      this is an invasive procedure which may increase the risk of contamination, patient
      discomfort and in some extreme cases blood sample collection may be a burden on patient
      haemoglobin levels which is prone to decrease in critical patients. Assessment is essential
      for determining whether action is required to change our existing resuscitation regime for
      critically ill burned patients. If the results show that the current resuscitation regime is
      suboptimal, then motivation for changing the existing practice can lead to improved clinical
      care and a reduction in over- or under resuscitation in the ICU environment with its
      potential harmful effects.

      The risks associated with participation can be considered negligible and the burden can be
      considered minimal in this observational study. The patients taking part in this study will
      have no direct benefit.
observational model: Case-Only
time perspective: Prospective
measure: Measurement of microcirculatory perfusion alterations in severe burns patients during standard fluid resuscitation.
time frame: Changes in perfusion parameters will be measured on admission (time zero, T=0), four hours after admission (T=4), eight hours after admission (T=8), twelve hours after admission (T=12) and twenty-four hours after admission (T=24
description: The main objective of our study is to measure standard microcirculatory perfusion parameters during standard resuscitation at different time points after a severe burn injury. These perfusion parameters are total vessel density (TVD), proportion of perfused vessels (PPV), functional capillary density (FCD) and focus depth.
measure: Microcirculatory perfusion alterations after administration of albumin.
time frame: Changes in microcirculatory perfusion parameters will be measured directly after administration of albumin. This will be 12 hours after starting fluid resuscitation.
description: Secondary objectives are to measure changes in standard microcirculatory parameters before and after administration of albumin. Albumin will be administered 12 hours after admission of the patient.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Can Ince, Prof
role: Study Director
affiliation: Erasmus Medical Center
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Burns