<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/NCT03795285</url>
  </required_header>
  <id_info>
    <org_study_id>Neonatal sepsis</org_study_id>
    <nct_id>NCT03795285</nct_id>
  </id_info>
  <brief_title>The Role of Neutrophil CD64 and Soluble Triggering Receptor Expressed on Myeloid Cells 1 in Neonatal Sepsis</brief_title>
  <official_title>The Role of Neutrophil CD64 and Soluble Triggering Receptor Expressed on Myeloid Cells 1 in Neonatal Sepsis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Neonatal sepsis (NS) is a rather serious but relatively common health problem. Despite recent&#xD;
      advances in the treatment of neonatal infection, mortality and comorbidities remain high.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neonatal sepsis is a major contributor to an estimated 2.6 million annual deaths and accounts&#xD;
      for approximately 3 % of all disability-adjusted life years. The consequences of NS can be&#xD;
      minimized by early initiation of antibiotic therapy. Due to high NS rates, the vulnerability&#xD;
      of the organism in the neonatal period and concerns about consequences (considerable&#xD;
      mortality, association with other acute or chronic complications), antibiotic therapy is&#xD;
      com¬monly started in clinical practice even though non-spe¬cific clinical signs develop. This&#xD;
      is in spite of the fact that antibiotic overuse is linked to major negative outcomes. The&#xD;
      reliable and early diagnosis of NS is therefore essential but, unfortunately, rather&#xD;
      difficult.&#xD;
&#xD;
      Probably the most widely used &quot;biochemical&quot; marker of NS, C-reactive protein (CRP), is one of&#xD;
      the so-called late markers. Its sensitivity is mainly low in the early stages of infection;&#xD;
      its reliability increases, particularly with serial measurements. In that case, its&#xD;
      negativity practically rules out the presence of NS. It is not completely specific for NS.&#xD;
      Procalcitonin (PCT), an intermediate marker, is relatively specific, providing prognostic&#xD;
      information as well; it decreases rapidly in response to effective therapy. However, its&#xD;
      complex postnatal &quot;physiological&quot; dynamics makes its measurements difficult, particularly in&#xD;
      early-onset sepsis.&#xD;
&#xD;
      CD64 is normally expressed in very low concentrations by unstimulated neutrophils. It is&#xD;
      considerably upregulated on the trigger of bacterial invasion and has been shown to be&#xD;
      involved in the process of phagocytosis and intracellular killing of pathogens. More&#xD;
      importantly, neutrophils from preterm infants express CD64 during bacterial infections to the&#xD;
      same degree as those from term infants, children, and adults. So in newborns, neutrophil CD64&#xD;
      have been found to be promising markers for diagnosis of early and late infections.&#xD;
&#xD;
      Among several candidate receptors, triggering Receptor Expressed on Myeloid cells 1 (TREM-1)&#xD;
      appears to play a relevant role in the modulation of innate immunity, amplifying or&#xD;
      attenuating Toll-Like Receptor (TLR)-induced signals. TREM-1 is a receptor of the&#xD;
      immunoglobulin superfamily, expressed on human neutrophils and monocytes. In the early phase&#xD;
      of infection, the engagements of Pattern Recognition Receptors (PRRs) by microbial components&#xD;
      induce up-regulation of TREM-1. After recognition of a still unknown ligand, TREM-1&#xD;
      associates with a signal transduction molecule called DAP12, triggering the sustained release&#xD;
      of pro-inflammatory cytokines (TNF-alpha and IL-1b) and chemokines (IL-8 and monocyte&#xD;
      chemotactic protein), which may result in prolonged survival of neutrophils and monocytes at&#xD;
      the inflammatory site.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 20, 2019</start_date>
  <completion_date type="Anticipated">September 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">September 20, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The mean difference of neutrophil CD64 expression and sTREM-1 before and after treatment</measure>
    <time_frame>72 hours</time_frame>
    <description>better understanding of neutrophil CD64 role as an essential player in pathogenesis of neonatal sepsis and the role of and sTREM-1 in pathogenesis of neonatal sepsis</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Neonatal SEPSIS</condition>
  <arm_group>
    <arm_group_label>Septic neonates:</arm_group_label>
    <description>fifty neonates with sepsis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls:</arm_group_label>
    <description>twenty healthy neonates.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Expression of neutrophil CD64</intervention_name>
    <description>Expression of neutrophil CD64 will be measured by Flow cytometry. In addition, sTREM-1 will be measured in the serum by ELISA</description>
    <arm_group_label>Controls:</arm_group_label>
    <arm_group_label>Septic neonates:</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Neonatal sepsis&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Sepsis was defined as a positive blood culture in infants with clinical and laboratory&#xD;
             findings of infection. Manifestations of sepsis include poor suckling, sleepiness,&#xD;
             respiratory distress, apnea, poor perfusion, cyanosis, bradycardia, fever or&#xD;
             hypothermia, feeding intolerance, and neurological signs (as seizures). Routine sepsis&#xD;
             evaluations included complete blood count, C-reactive protein, and blood culture.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  malformations&#xD;
&#xD;
          -  prematurity&#xD;
&#xD;
          -  Apgar score less than seven&#xD;
&#xD;
          -  on antibiotics treatment before the start of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>50 Days</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>reham elmahdy</last_name>
    <phone>+201002714637</phone>
    <email>reham.elmahdy@aun.edu.eg</email>
  </overall_contact>
  <reference>
    <citation>Halek J, Novak M, Medkova A, Furst T, Juranova J. The role of nCD64 in the diagnosis of neonatal sepsis in preterm newborns. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2018 Jun 21. doi: 10.5507/bp.2018.033. Online ahead of print.</citation>
    <PMID>29955185</PMID>
  </reference>
  <reference>
    <citation>Wright JK, Hayford K, Tran V, Al Kibria GM, Baqui A, Manajjir A, Mahmud A, Begum N, Siddiquee M, Kain KC, Farzin A. Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched case-control study. BMC Pediatr. 2018 Mar 23;18(1):118. doi: 10.1186/s12887-018-1087-x.</citation>
    <PMID>29571293</PMID>
  </reference>
  <reference>
    <citation>Ford JW, McVicar DW. TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol. 2009 Feb;21(1):38-46. doi: 10.1016/j.coi.2009.01.009. Epub 2009 Feb 21.</citation>
    <PMID>19230638</PMID>
  </reference>
  <reference>
    <citation>Groselj-Grenc M, Ihan A, Derganc M. Neutrophil and monocyte CD64 and CD163 expression in critically ill neonates and children with sepsis: comparison of fluorescence intensities and calculated indexes. Mediators Inflamm. 2008;2008:202646. doi: 10.1155/2008/202646.</citation>
    <PMID>18604302</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>January 5, 2019</last_update_submitted>
  <last_update_submitted_qc>January 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Reham I El-mahdy</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Early onset sepsis</keyword>
  <keyword>sTREM-1</keyword>
  <keyword>Neutrophil CD64</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Neonatal Sepsis</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/NCT03795285
org study id: Neonatal sepsis
nct id: NCT03795285
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Neonatal sepsis (NS) is a rather serious but relatively common health problem. Despite recent
      advances in the treatment of neonatal infection, mortality and comorbidities remain high.
Neonatal sepsis is a major contributor to an estimated 2.6 million annual deaths and accounts
      for approximately 3 % of all disability-adjusted life years. The consequences of NS can be
      minimized by early initiation of antibiotic therapy. Due to high NS rates, the vulnerability
      of the organism in the neonatal period and concerns about consequences (considerable
      mortality, association with other acute or chronic complications), antibiotic therapy is
      com¬monly started in clinical practice even though non-spe¬cific clinical signs develop. This
      is in spite of the fact that antibiotic overuse is linked to major negative outcomes. The
      reliable and early diagnosis of NS is therefore essential but, unfortunately, rather
      difficult.

      Probably the most widely used "biochemical" marker of NS, C-reactive protein (CRP), is one of
      the so-called late markers. Its sensitivity is mainly low in the early stages of infection;
      its reliability increases, particularly with serial measurements. In that case, its
      negativity practically rules out the presence of NS. It is not completely specific for NS.
      Procalcitonin (PCT), an intermediate marker, is relatively specific, providing prognostic
      information as well; it decreases rapidly in response to effective therapy. However, its
      complex postnatal "physiological" dynamics makes its measurements difficult, particularly in
      early-onset sepsis.

      CD64 is normally expressed in very low concentrations by unstimulated neutrophils. It is
      considerably upregulated on the trigger of bacterial invasion and has been shown to be
      involved in the process of phagocytosis and intracellular killing of pathogens. More
      importantly, neutrophils from preterm infants express CD64 during bacterial infections to the
      same degree as those from term infants, children, and adults. So in newborns, neutrophil CD64
      have been found to be promising markers for diagnosis of early and late infections.

      Among several candidate receptors, triggering Receptor Expressed on Myeloid cells 1 (TREM-1)
      appears to play a relevant role in the modulation of innate immunity, amplifying or
      attenuating Toll-Like Receptor (TLR)-induced signals. TREM-1 is a receptor of the
      immunoglobulin superfamily, expressed on human neutrophils and monocytes. In the early phase
      of infection, the engagements of Pattern Recognition Receptors (PRRs) by microbial components
      induce up-regulation of TREM-1. After recognition of a still unknown ligand, TREM-1
      associates with a signal transduction molecule called DAP12, triggering the sustained release
      of pro-inflammatory cytokines (TNF-alpha and IL-1b) and chemokines (IL-8 and monocyte
      chemotactic protein), which may result in prolonged survival of neutrophils and monocytes at
      the inflammatory site.
observational model: Case-Control
time perspective: Prospective
measure: The mean difference of neutrophil CD64 expression and sTREM-1 before and after treatment
time frame: 72 hours
description: better understanding of neutrophil CD64 role as an essential player in pathogenesis of neonatal sepsis and the role of and sTREM-1 in pathogenesis of neonatal sepsis
arm group label: Septic neonates:
description: fifty neonates with sepsis.
arm group label: Controls:
description: twenty healthy neonates.
intervention type: Diagnostic Test
intervention name: Expression of neutrophil CD64
description: Expression of neutrophil CD64 will be measured by Flow cytometry. In addition, sTREM-1 will be measured in the serum by ELISA
arm group label: Controls:
arm group label: Septic neonates:
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Day
maximum age: 50 Days
last name: reham elmahdy
phone: +201002714637
email: reham.elmahdy@aun.edu.eg
citation: Halek J, Novak M, Medkova A, Furst T, Juranova J. The role of nCD64 in the diagnosis of neonatal sepsis in preterm newborns. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2018 Jun 21. doi: 10.5507/bp.2018.033. Online ahead of print.
PMID: 29955185
citation: Wright JK, Hayford K, Tran V, Al Kibria GM, Baqui A, Manajjir A, Mahmud A, Begum N, Siddiquee M, Kain KC, Farzin A. Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched case-control study. BMC Pediatr. 2018 Mar 23;18(1):118. doi: 10.1186/s12887-018-1087-x.
PMID: 29571293
citation: Ford JW, McVicar DW. TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol. 2009 Feb;21(1):38-46. doi: 10.1016/j.coi.2009.01.009. Epub 2009 Feb 21.
PMID: 19230638
citation: Groselj-Grenc M, Ihan A, Derganc M. Neutrophil and monocyte CD64 and CD163 expression in critically ill neonates and children with sepsis: comparison of fluorescence intensities and calculated indexes. Mediators Inflamm. 2008;2008:202646. doi: 10.1155/2008/202646.
PMID: 18604302
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Reham I El-mahdy
investigator title: Principal Investigator
mesh term: Sepsis
mesh term: Toxemia
mesh term: Neonatal Sepsis