<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/NCT03782454</url>
  </required_header>
  <id_info>
    <org_study_id>JS008</org_study_id>
    <nct_id>NCT03782454</nct_id>
  </id_info>
  <brief_title>Quantification of Bacterial DNA in Sepsis</brief_title>
  <official_title>Quantification of Bacterial DNA in Septic Intensive Care Patients in Relation to Concentration of Antibiotics and Clinical Outcome: A Prospective Observation Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Region Örebro County</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Region Örebro County</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>
      The purpose of this study is to evaluate whether bacterial DNA clearance measured with&#xD;
      droplet digital Polymerase Chain Reaction (ddPCR) can be used as a measure of bacterial load&#xD;
      in septic intensive care patients. Furthermore, the aim is to examine a possible relation&#xD;
      between clearance of bacterial DNA and clinical outcome in the septic patient, and the&#xD;
      relationship between concentration of beta-lactam antibiotics and the clearance of bacterial&#xD;
      DNA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Septic syndrome caused by bloodstream infections represents a major healthcare problem&#xD;
      worldwide and is the leading cause of mortality in the non-cardiac intensive care unit (ICU).&#xD;
      Despite ongoing research efforts in sepsis, the mortality remains as high as 12-30%.&#xD;
&#xD;
      In severe sepsis, the time to adequate antibiotic therapy has been clearly linked to&#xD;
      survival. However, in the emergency room, it is challenging to identify the cause behind the&#xD;
      clinical presentation and identify patients who would benefit the most from antibiotic&#xD;
      treatment. An indiscriminate use of antibiotics inevitably leads to bacterial resistance and&#xD;
      unacceptable adverse events. Thus, there is a great and unmet medical need to develop novel&#xD;
      diagnostic instruments that could inform the clinician about who would need antibiotics and&#xD;
      who would not benefit from it. Furthermore, early identification of the causal microorganism&#xD;
      and the inflammatory status of the patients would improve decisions about treatments and&#xD;
      reduce administration of antibiotics.&#xD;
&#xD;
      Today the gold standard for diagnosis of bloodstream infections (BSI) is blood culture&#xD;
      followed by identification of species and resistance pattern by standard laboratory&#xD;
      procedures. This procedure is associated with a high specificity but also with a low&#xD;
      sensitivity. Probable reasons for a negative blood culture despite a strong clinical&#xD;
      suspicion could be insufficient blood volume in the culture bottles or antibiotic treatment&#xD;
      prior to blood sampling with a subsequent failure of the bacteria to grow in the bottles.&#xD;
&#xD;
      In recent years Polymerase Chain reaction (PCR) has been proposed as a method to determine&#xD;
      bacterial DNA based on amplification of specific subunits (16S and 18S) of bacterial&#xD;
      ribosomal RNA. PCR require very small amount of DNA. Another advantage is the possibility to&#xD;
      determine bacterial species from non-viable bacteria by multiplex PCRs. However most of those&#xD;
      multiplex PCRs have shown a limited sensitivity even though they also found clinical relevant&#xD;
      pathogens that were not detected with blood cultures. Another limitation is that&#xD;
      multiplex-PCR only detects at maximum 95% of all sepsis causing pathogens. In a recent&#xD;
      published study the author concluded that a tested multiplex PCR &quot;on whole blood specimens&quot;&#xD;
      in adjunct to current culture-based methods provided a clinical add-on value. The future role&#xD;
      of PCR and other molecular techniques in the clinical setting needs further evaluation.&#xD;
&#xD;
      A new method that could improve the diagnostics of sepsis and also have the possibility to&#xD;
      follow the bacterial DNA load during antibiotic treatment is Droplet Digital PCR (ddPCR).&#xD;
      This technique enables an absolute quantification of the sepsis causing pathogen targeting&#xD;
      either a species specific gene or the 16S ribosomal DNA (rDNA) gene, present in several&#xD;
      copies per bacteria. In ddPCR, the sample is divided into about 20.000 water-in-oil droplets,&#xD;
      and in all of them the PCR-reaction occurs. Following PCR, each droplet is analyzed to&#xD;
      determine the fraction of PCR-positive droplets giving the amount of bacterial DNA in the&#xD;
      original sample. The absolute target DNA template concentration can then be calculated, since&#xD;
      the size of the droplets is known, and by using Poisson distribution statistics for the&#xD;
      correction of more than one positive reaction in the same droplet.&#xD;
&#xD;
      To identify the sepsis causing pathogen sequencing of the 16S rDNA gene or a shotgun&#xD;
      metagenomics approach could be used. In the latter, all DNA in a sample is sequenced using&#xD;
      Next Generation Sequencing (NGS) and the sepsis causing pathogen can be both detected and&#xD;
      aims to be quantified through bioinformatics data analysis.&#xD;
&#xD;
      During the septic course the patient go from vasodilation to vascular leakage and finally a&#xD;
      hypotension. This together with added intravenous fluid treatment will increase the&#xD;
      distribution volume with an altered pharmacokinetic state for added antibiotics. Furthermore,&#xD;
      decreased kidney function is common in ICU patients and augmented creatinine clearance during&#xD;
      the acute phase of sepsis is described with increasing frequency. Therefore, it is difficult&#xD;
      to anticipate the optimal antibiotic dose for the septic patient. Indeed, it is shown that in&#xD;
      a considerable portion of ICU patients an adequate antibiotic exposure is not achieved and&#xD;
      this is associated with negative clinical outcome.&#xD;
&#xD;
      A dysregulated host response is a cornerstone of the current understanding of sepsis&#xD;
      pathophysiology. Initially during the sepsis course a proinflammatory response is induced by&#xD;
      early activation genes, including cytokines associated with inflammation: tumor necrosis&#xD;
      factor (TNF), Interleukin-1(IL-1), IL-12 and IL-18. Simultaneously an immune suppression is&#xD;
      induced by anti-inflammatory cytokines i.e IL-10 and transforming growth factor. A disrupted&#xD;
      homeostasis of the pro- and anti-inflammatory response is suggested to be part of the&#xD;
      dysregulated host response in sepsis although clinically available biomarkers for its&#xD;
      identification are lacking. Furthermore, the regulatory mediators involved in this process&#xD;
      and the association to bacterial clearance during sepsis needs further investigation.&#xD;
&#xD;
      The gastrointestinal tract may be a source of bacteria and a worsening of the septic&#xD;
      inflammation in ICU patients, if the epithelial barrier is disrupted. Thus intact&#xD;
      gastrointestinal function is critical in severely diseased patients. There are no clinically&#xD;
      available biomarkers of gastrointestinal function; however the recently described acute&#xD;
      gastrointestinal injury (AGI) score has been shown to correlate with adverse outcome in&#xD;
      ICU-patients.&#xD;
&#xD;
      The aim of the study is to investigate whether bacterial DNA in whole blood measured with&#xD;
      ddPCR can be used for assessment of bacterial clearance in septic intensive care patients. To&#xD;
      do so the investigators will search for a potential association between bacterial DNA&#xD;
      clearance and clearance of bacteremia detected by blood cultures.&#xD;
&#xD;
      Further, the aim is to examine a possible relation between clearance of bacterial DNA,&#xD;
      biomarkers of dysregulated host response, and clinical outcome in the septic patient. Outcome&#xD;
      is measured as: mortality on ICU, mortality &lt;28 days, days in the ICU, change in Sequential&#xD;
      Organ Failure Assessment score(SOFA), time in assisted ventilation, lactate clearance, need&#xD;
      of vasopressors, and severity of gastrointestinal injury. Further, the aim is to study the&#xD;
      relationship between concentration of beta-lactam antibiotics i.e. the minimal inhibitory&#xD;
      concentration for the bacteria (T&gt;MIC) detected and the clearance of bacterial DNA. The&#xD;
      material collected will also contribute to reveal the relationship between ddPCR and shot gun&#xD;
      sequencing in detecting the sepsis causing bacteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 7, 2019</start_date>
  <completion_date type="Anticipated">May 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>Bacterial DNA measured by 16S ddPCR</measure>
    <time_frame>48 hours</time_frame>
    <description>copies/mL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentration of beta-lactam antibiotics</measure>
    <time_frame>48 hours</time_frame>
    <description>mg/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lactate clearance</measure>
    <time_frame>48 hours</time_frame>
    <description>mmol/L, clearance %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SOFA</measure>
    <time_frame>ICU stay up to 30 days</time_frame>
    <description>Sequential Organ Failure Assessment score, from 0(normal) to 24(highest organ dysfunction)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in assisted ventilation</measure>
    <time_frame>ICU stay up to 30 days</time_frame>
    <description>hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need of vasopressors</measure>
    <time_frame>ICU stay up to 30 days</time_frame>
    <description>mcg/kg/hour</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days in the ICU</measure>
    <time_frame>ICU stay up to 30 days</time_frame>
    <description>Days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AGI score</measure>
    <time_frame>ICU stay up to 30 days</time_frame>
    <description>Acute Gastrointestinal Injury Score 0(normal) to 4(life-threatening GI complications)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU mortality</measure>
    <time_frame>ICU stay up to 30 days</time_frame>
    <description>Occurence of death during ICU stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>28-day mortality</measure>
    <time_frame>28 days</time_frame>
    <description>Occurence of death at day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal complications</measure>
    <time_frame>28 days</time_frame>
    <description>Occurence of gastrointestinal complications including GI-bleeding, GI-ischemia, pancreatitis and ileus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intestinal fatty acid binding protein (I-FABP)</measure>
    <time_frame>48 hours</time_frame>
    <description>picogram/mL, biomarker of gastrointestinal injury</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Citrulline</measure>
    <time_frame>48 hours</time_frame>
    <description>nmol/mL, biomarker of gastrointestinal injury</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nuclear DNA</measure>
    <time_frame>48 hours</time_frame>
    <description>copies/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokines (Th1 and Th2 signature panel)</measure>
    <time_frame>48 hours</time_frame>
    <description>pg/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood cell populations</measure>
    <time_frame>48 hours</time_frame>
    <description>Mean fluorescence intensity/ Antibodies/cell. Monocytes, granulocytes, T-cells, and myeloid derived stem cells including surface markers such as PD-1(Programmed cell death protein 1),PD-L1 (Programmed death ligand 1), and HLA-DR (Human leukocyte Antigen - DR isotype)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HLA-DR messenger RNA (mRNA)</measure>
    <time_frame>48 hours</time_frame>
    <description>ratio/reference gene</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procalcitonin</measure>
    <time_frame>48 hours</time_frame>
    <description>mcg/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MicroRNA (miRNA)</measure>
    <time_frame>48 hours</time_frame>
    <description>Relative expression/ratio reference gene, transcriptomic and quantitative PCR based measurement</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Septic Shock</condition>
  <condition>Sepsis Bacterial</condition>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>intensive care patients with sepsis</arm_group_label>
    <description>Adult patients with verified or suspected sepsis admitted to the intensive care department from the emergency department</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood sampling</intervention_name>
    <description>Blood samples taken every third hour during the first 48 hours of intensive care</description>
    <arm_group_label>intensive care patients with sepsis</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood, serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients at the emergency department&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patient at the emergency department with verified or suspected sepsis and who is&#xD;
             in need of intensive care.&#xD;
&#xD;
          2. Informed Consent by patient or legal representative.&#xD;
&#xD;
          3. Indication for beta-lactam antibiotics&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. &lt; 18 years&#xD;
&#xD;
          2. Patients and/or relatives unable to understand study information.&#xD;
&#xD;
          3. Anaphylactic allergy to beta-lactam antibiotics&#xD;
&#xD;
          4. Patients already treated with antibiotics&#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>Jan Källman, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Region Örebro County</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hans Hjelmqvist, Phd</last_name>
    <role>Principal Investigator</role>
    <affiliation>Region Örebro County</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Johanna Savilampi, PhD</last_name>
    <phone>+460196020266</phone>
    <email>johanna.savilampi@regionorebrolan.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Karolina Liljedahl Pryz, MD</last_name>
    <phone>+460196020000</phone>
    <email>karolina.liljedahl.pryz@regionorebrolan.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital in Örebro</name>
      <address>
        <city>Örebro</city>
        <zip>701 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Johanna Savilampi, MD</last_name>
      <phone>+46196020266</phone>
      <email>johanna.savilampi@orebroll.se</email>
    </contact>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>January 28, 2019</last_update_submitted>
  <last_update_submitted_qc>January 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bacterial DNA clearance</keyword>
  <keyword>Droplet digital PCR</keyword>
  <keyword>Betalactam antibiotics</keyword>
  <keyword>Acute gastrointestinal index</keyword>
  <keyword>Cytokines</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03782454
org study id: JS008
nct id: NCT03782454
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate whether bacterial DNA clearance measured with
      droplet digital Polymerase Chain Reaction (ddPCR) can be used as a measure of bacterial load
      in septic intensive care patients. Furthermore, the aim is to examine a possible relation
      between clearance of bacterial DNA and clinical outcome in the septic patient, and the
      relationship between concentration of beta-lactam antibiotics and the clearance of bacterial
      DNA.
Septic syndrome caused by bloodstream infections represents a major healthcare problem
      worldwide and is the leading cause of mortality in the non-cardiac intensive care unit (ICU).
      Despite ongoing research efforts in sepsis, the mortality remains as high as 12-30%.

      In severe sepsis, the time to adequate antibiotic therapy has been clearly linked to
      survival. However, in the emergency room, it is challenging to identify the cause behind the
      clinical presentation and identify patients who would benefit the most from antibiotic
      treatment. An indiscriminate use of antibiotics inevitably leads to bacterial resistance and
      unacceptable adverse events. Thus, there is a great and unmet medical need to develop novel
      diagnostic instruments that could inform the clinician about who would need antibiotics and
      who would not benefit from it. Furthermore, early identification of the causal microorganism
      and the inflammatory status of the patients would improve decisions about treatments and
      reduce administration of antibiotics.

      Today the gold standard for diagnosis of bloodstream infections (BSI) is blood culture
      followed by identification of species and resistance pattern by standard laboratory
      procedures. This procedure is associated with a high specificity but also with a low
      sensitivity. Probable reasons for a negative blood culture despite a strong clinical
      suspicion could be insufficient blood volume in the culture bottles or antibiotic treatment
      prior to blood sampling with a subsequent failure of the bacteria to grow in the bottles.

      In recent years Polymerase Chain reaction (PCR) has been proposed as a method to determine
      bacterial DNA based on amplification of specific subunits (16S and 18S) of bacterial
      ribosomal RNA. PCR require very small amount of DNA. Another advantage is the possibility to
      determine bacterial species from non-viable bacteria by multiplex PCRs. However most of those
      multiplex PCRs have shown a limited sensitivity even though they also found clinical relevant
      pathogens that were not detected with blood cultures. Another limitation is that
      multiplex-PCR only detects at maximum 95% of all sepsis causing pathogens. In a recent
      published study the author concluded that a tested multiplex PCR "on whole blood specimens"
      in adjunct to current culture-based methods provided a clinical add-on value. The future role
      of PCR and other molecular techniques in the clinical setting needs further evaluation.

      A new method that could improve the diagnostics of sepsis and also have the possibility to
      follow the bacterial DNA load during antibiotic treatment is Droplet Digital PCR (ddPCR).
      This technique enables an absolute quantification of the sepsis causing pathogen targeting
      either a species specific gene or the 16S ribosomal DNA (rDNA) gene, present in several
      copies per bacteria. In ddPCR, the sample is divided into about 20.000 water-in-oil droplets,
      and in all of them the PCR-reaction occurs. Following PCR, each droplet is analyzed to
      determine the fraction of PCR-positive droplets giving the amount of bacterial DNA in the
      original sample. The absolute target DNA template concentration can then be calculated, since
      the size of the droplets is known, and by using Poisson distribution statistics for the
      correction of more than one positive reaction in the same droplet.

      To identify the sepsis causing pathogen sequencing of the 16S rDNA gene or a shotgun
      metagenomics approach could be used. In the latter, all DNA in a sample is sequenced using
      Next Generation Sequencing (NGS) and the sepsis causing pathogen can be both detected and
      aims to be quantified through bioinformatics data analysis.

      During the septic course the patient go from vasodilation to vascular leakage and finally a
      hypotension. This together with added intravenous fluid treatment will increase the
      distribution volume with an altered pharmacokinetic state for added antibiotics. Furthermore,
      decreased kidney function is common in ICU patients and augmented creatinine clearance during
      the acute phase of sepsis is described with increasing frequency. Therefore, it is difficult
      to anticipate the optimal antibiotic dose for the septic patient. Indeed, it is shown that in
      a considerable portion of ICU patients an adequate antibiotic exposure is not achieved and
      this is associated with negative clinical outcome.

      A dysregulated host response is a cornerstone of the current understanding of sepsis
      pathophysiology. Initially during the sepsis course a proinflammatory response is induced by
      early activation genes, including cytokines associated with inflammation: tumor necrosis
      factor (TNF), Interleukin-1(IL-1), IL-12 and IL-18. Simultaneously an immune suppression is
      induced by anti-inflammatory cytokines i.e IL-10 and transforming growth factor. A disrupted
      homeostasis of the pro- and anti-inflammatory response is suggested to be part of the
      dysregulated host response in sepsis although clinically available biomarkers for its
      identification are lacking. Furthermore, the regulatory mediators involved in this process
      and the association to bacterial clearance during sepsis needs further investigation.

      The gastrointestinal tract may be a source of bacteria and a worsening of the septic
      inflammation in ICU patients, if the epithelial barrier is disrupted. Thus intact
      gastrointestinal function is critical in severely diseased patients. There are no clinically
      available biomarkers of gastrointestinal function; however the recently described acute
      gastrointestinal injury (AGI) score has been shown to correlate with adverse outcome in
      ICU-patients.

      The aim of the study is to investigate whether bacterial DNA in whole blood measured with
      ddPCR can be used for assessment of bacterial clearance in septic intensive care patients. To
      do so the investigators will search for a potential association between bacterial DNA
      clearance and clearance of bacteremia detected by blood cultures.

      Further, the aim is to examine a possible relation between clearance of bacterial DNA,
      biomarkers of dysregulated host response, and clinical outcome in the septic patient. Outcome
      is measured as: mortality on ICU, mortality <28 days, days in the ICU, change in Sequential
      Organ Failure Assessment score(SOFA), time in assisted ventilation, lactate clearance, need
      of vasopressors, and severity of gastrointestinal injury. Further, the aim is to study the
      relationship between concentration of beta-lactam antibiotics i.e. the minimal inhibitory
      concentration for the bacteria (T>MIC) detected and the clearance of bacterial DNA. The
      material collected will also contribute to reveal the relationship between ddPCR and shot gun
      sequencing in detecting the sepsis causing bacteria.
observational model: Cohort
time perspective: Prospective
measure: Bacterial DNA measured by 16S ddPCR
time frame: 48 hours
description: copies/mL
measure: Concentration of beta-lactam antibiotics
time frame: 48 hours
description: mg/mL
measure: Lactate clearance
time frame: 48 hours
description: mmol/L, clearance %
measure: SOFA
time frame: ICU stay up to 30 days
description: Sequential Organ Failure Assessment score, from 0(normal) to 24(highest organ dysfunction)
measure: Time in assisted ventilation
time frame: ICU stay up to 30 days
description: hours
measure: Need of vasopressors
time frame: ICU stay up to 30 days
description: mcg/kg/hour
measure: Days in the ICU
time frame: ICU stay up to 30 days
description: Days
measure: AGI score
time frame: ICU stay up to 30 days
description: Acute Gastrointestinal Injury Score 0(normal) to 4(life-threatening GI complications)
measure: ICU mortality
time frame: ICU stay up to 30 days
description: Occurence of death during ICU stay
measure: 28-day mortality
time frame: 28 days
description: Occurence of death at day 28
measure: Gastrointestinal complications
time frame: 28 days
description: Occurence of gastrointestinal complications including GI-bleeding, GI-ischemia, pancreatitis and ileus
measure: Intestinal fatty acid binding protein (I-FABP)
time frame: 48 hours
description: picogram/mL, biomarker of gastrointestinal injury
measure: Citrulline
time frame: 48 hours
description: nmol/mL, biomarker of gastrointestinal injury
measure: Nuclear DNA
time frame: 48 hours
description: copies/mL
measure: Cytokines (Th1 and Th2 signature panel)
time frame: 48 hours
description: pg/ml
measure: Blood cell populations
time frame: 48 hours
description: Mean fluorescence intensity/ Antibodies/cell. Monocytes, granulocytes, T-cells, and myeloid derived stem cells including surface markers such as PD-1(Programmed cell death protein 1),PD-L1 (Programmed death ligand 1), and HLA-DR (Human leukocyte Antigen - DR isotype)
measure: HLA-DR messenger RNA (mRNA)
time frame: 48 hours
description: ratio/reference gene
measure: Procalcitonin
time frame: 48 hours
description: mcg/L
measure: MicroRNA (miRNA)
time frame: 48 hours
description: Relative expression/ratio reference gene, transcriptomic and quantitative PCR based measurement
arm group label: intensive care patients with sepsis
description: Adult patients with verified or suspected sepsis admitted to the intensive care department from the emergency department
intervention type: Diagnostic Test
intervention name: Blood sampling
description: Blood samples taken every third hour during the first 48 hours of intensive care
arm group label: intensive care patients with sepsis
whole blood, serum
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jan Källman, PhD
role: Principal Investigator
affiliation: Region Örebro County
last name: Hans Hjelmqvist, Phd
role: Principal Investigator
affiliation: Region Örebro County
last name: Johanna Savilampi, PhD
phone: +460196020266
email: johanna.savilampi@regionorebrolan.se
last name: Karolina Liljedahl Pryz, MD
phone: +460196020000
email: karolina.liljedahl.pryz@regionorebrolan.se
facility: 
status: Recruiting
contact: 
country: Sweden
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
sharing ipd: Undecided