Neonatal SEPSISNCT03795285
The Role of Neutrophil CD64 and Soluble Triggering Receptor Expressed on Myeloid Cells 1 in Neonatal Sepsis
An observational study of Neonatal SEPSIS, run by Assiut University.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 day to 50 days
- Conditions the study is for
- Neonatal SEPSIS
- What is being tested?
- Expression of neutrophil CD64
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 20 Feb 2019to 30 Sep 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 50 days
- All sexes
- Child
Study population: Neonatal sepsis
Who may be able to join
- Sepsis was defined as a positive blood culture in infants with clinical and laboratory findings of infection. Manifestations of sepsis include poor suckling, sleepiness, respiratory distress, apnea, poor perfusion, cyanosis, bradycardia, fever or hypothermia, feeding intolerance, and neurological signs (as seizures). Routine sepsis evaluations included complete blood count, C-reactive protein, and blood culture.
Who cannot join
- malformations
- prematurity
- Apgar score less than seven
- on antibiotics treatment before the start of the study
Trial locations and contacts
No sites are listed yet.
About this study
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.
Read the detailed description
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.
- Conditions
- Neonatal SEPSIS
- Being tested
- Expression of neutrophil CD64
- Keywords
- Early onset sepsis, sTREM-1, Neutrophil CD64
- Medical subject headings
- Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Expression of neutrophil CD64Diagnostic test
Expression of neutrophil CD64 will be measured by Flow cytometry. In addition, sTREM-1 will be measured in the serum by ELISA
| Study group | Role | What they receive |
|---|---|---|
| Septic neonates: | fifty neonates with sepsis. Receives: Diagnostic Test: Expression of neutrophil CD64 | |
| Controls: | twenty healthy neonates. Receives: Diagnostic Test: Expression of neutrophil CD64 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The mean difference of neutrophil CD64 expression and sTREM-1 before and after treatment
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
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2019
- Study start20 Feb 2019 (estimated)
- Primary completion20 Sep 2019 (estimated)
- Study completion30 Sep 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Neonatal SEPSISStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Reham I El-mahdy, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03795285
- Sponsor's protocol ID
- Neonatal sepsis
- Status last verified
- Jan 2019
- First submitted
- 4 Jan 2019
- Last updated
- 8 Jan 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 29955185Wright 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.
PubMed 29571293Ford 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.
PubMed 19230638Groselj-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.
PubMed 18604302
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Neutrophil CD64 and Soluble Triggering Receptor Expressed on Myeloid Cells 1 in Neonatal Sepsis
- ClinicalTrials.gov ID
- NCT03795285
- Acronym / sponsor ID
- Neonatal sepsis
- Conditions
- Neonatal SEPSIS
- Keywords
- Early onset sepsis, sTREM-1, Neutrophil CD64
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 20 Feb 2019 (estimated)
- Primary completion
- 20 Sep 2019 (estimated)
- Study completion
- 30 Sep 2019 (estimated)
- First posted
- 7 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Septic neonates: | – | Diagnostic Test: Expression of neutrophil CD64fifty neonates with sepsis. |
| Controls: | – | Diagnostic Test: Expression of neutrophil CD64twenty healthy neonates. |
Who may qualify
- Ages
- 1 day to 50 days
- Sex
- All
- Age groups
- Child
- Study population
- Neonatal sepsis
Key inclusion criteria (1 listed)
- Sepsis was defined as a positive blood culture in infants with clinical and laboratory findings of infection. Manifestations of sepsis include poor suckling, sleepiness, respiratory distress, apnea, poor perfusion, cyanosis, bradycardia, fever or hypothermia, feeding intolerance, and neurological signs (as seizures). Routine sepsis evaluations included complete blood count, C-reactive protein, and blood culture.
Key exclusion criteria (4 listed)
- malformations
- prematurity
- Apgar score less than seven
- on antibiotics treatment before the start of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Expression of neutrophil CD64Expression of neutrophil CD64 will be measured by Flow cytometry. In addition, sTREM-1 will be measured in the serum by ELISA | Diagnostic test | Controls:, Septic neonates: |
Primary outcome
The mean difference of neutrophil CD64 expression and sTREM-1 before and after treatment
Time frame: 72 hours
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Background: PubMed 29955185Halek 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.
- Background: PubMed 29571293Wright 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.
- Background: PubMed 19230638Ford 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.
- Background: PubMed 18604302Groselj-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of Neonatal SEPSIS, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact reham elmahdy (+201002714637, reham.elmahdy@aun.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The mean difference of neutrophil CD64 expression and sTREM-1 before and after treatment (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03795285, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.