Molecular Culture for the Diagnosis of Neonatal Sepsis

NCT05763680 | Unknown

• 1 other identifier: W22_453
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Early diagnosis of sepsis in neonates is complicated as the signs and symptoms are nonspecific. Although blood culture is the gold standard for the diagnosis, false-negative results and long incubation period of 36-72 hours limits the use of blood culture to rule out sepsis at initial suspicion. Since delay in diagnosis may lead to progressive deterioration, antibiotics are often started empirically at initial sepsis suspicion, awaiting results of the blood culture. Consequently, uninfected infants are often unnecessarily exposed to empirical antibiotics. To reduce unnecessary treatment of non-infected infants, an early, sensitive and specific diagnostic tool would be helpful to guide clinicians faster when to discontinue antibiotics. Molecular Culture (MC) via IS-pro is a novel, advanced, molecular culture technique which is able to culture bacteria within 4 hours after blood sampling. MC might thus be a potential diagnostic tool to detect or rule out sepsis in infants quickly, however data on MC for diagnosis of sepsis in this population is limited. Objective: The aim of this study is to evaluate whether MC is of additive predictive value for the diagnosis sepsis in this vulnerable group. Study design: Prospective observational cohort study. Study population: All infants suspected for neonatal sepsis of both early and late onset will be eligible for study participation. They will be treated according to the standard local guidelines. Intervention (if applicable): In case of a suspicion of sepsis at birth, blood will be collected for a conventional blood culture as part of standard care. Additionally, a blood sample will be collected from the umbilical cord for MC. In case of a suspicion of sepsis not directly postpartum, an additional blood sample will be taken for MC analysis, directly following sampling for conventional culture, implying no extra phlebotomy. Main study parameters/endpoints: The main study parameter is the discordance in positive and negative outcomes of MC compared to outcomes of conventional blood culture. As the diagnostic accuracy of the conventional blood culture (the current gold standard) is being questioned, the predictive value of MC versus conventional blood culture towards clinical sepsis will also be tested.

Conditions

Neonatal Sepsis, Early-Onset; Culture Positive Neonatal Sepsis; Culture Negative Neonatal Sepsis; Clinical Sepsis; Microbial Disease; Neonatal Infection; Microbial Colonization; Neonatal Sepsis, Late-Onset

Outcome Measures

Primary Outcomes (1)

• Comparison of Molecular Culture results to traditional culture

  Molecular Culture assay will be performed on umbilical cord blood samples and peripherally sampled blood. Results will be compared to conventional peripheral blood cultures that are taken from infants who receive a work up for sepsis. Test characteristics, such as sensitivity, specificity, as well as positive and negative predictive values will be given.

  The outcome measure will be assessed after study completion, approximately 2 years after start of inclusion

Secondary Outcomes (1)

• Comparison of diagnostic accuracy of Molecular Culture for clinical neonatal sepsis versus conventional peripheral culture

  The outcome measure will be assessed after study completion, approximately 2 years after start of inclusion

Study Arms (1)

Infants suspect of neonatal sepsis (early and late onset) up to 90 days postnatally

Infants who are suspect of sepsis, either based on risk factors for infection or on clinical assessment. No restrictions in terms of gestational age

Diagnostic Test: Molecular Culture

Interventions

Molecular Culture DIAGNOSTIC_TEST

PCR based technique that amplifies the interspace region in bacterial DNA, that is located between the genes coding for 16S and 23S ribosomal subunits. Primers are used for the majority of known pathogenic phyla, i.e. FAFV, Bacteroidetes, Firmicutes and Proteobacteria. The nucleotide length of the Interspace region is species specific for bacterial single species. Bacteria all have one or multiple alleles for this interspace region. The combination of the amount of alleles, as well as the nucleotide strand length, makes for a specific profile that is distinctive for the species. Available software is able to match this profile to a particular pathogen, enabling confirmation and identification of bacteria in samples within 5 hours in our experimental workflow.

Also known as: IS Pro

Infants suspect of neonatal sepsis (early and late onset) up to 90 days postnatally

Eligibility Criteria

• Age: Up to 90 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Infants who are admitted to a clinical ward, either delivery or varying levels of neonatal wards.

You may qualify if:

• Gestational age \>24 weeks
• Neonates who receive a work up for early onset sepsis (including blood sampling for conventional culture) , either based on risk factors or clinical signs (according to local treatment guidelines) OR
• Infants who receive a work (including blood sampling for conventional culture) up for late onset sepsis

You may not qualify if:

• For neonates suspicious of having early onset sepsis: congenital TORCHES infection (Toxoplasma gondii, Rubella virus, Cytomegalovirus, Herpes simplex virus and Treponema pallidum (Syphilis)

Sponsors & Collaborators

• Jip Groen: lead
• InBiome: collaborator

Study Sites (1)

Maxima Medisch Centrum

Veldhoven, Netherlands

RECRUITING

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples, taken from the umbilical cord postpartum Blood samples, taken peripherally directly following sampling for conventional culture. Bacterial swabs, taken from blood sample sites on the umbilical cord to detect possible contaminants

MeSH Terms

Conditions

Neonatal Sepsis; Communicable Diseases

Condition Hierarchy (Ancestors)

Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Tim GJ de Meij, MD, PhD

  Pediatric Gastro-enterologist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jip Groen, MD

CONTACT

+31614493808; j.groen5@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: March 10, 2023
• Study Start: July 15, 2023
• Primary Completion: March 1, 2025
• Study Completion: August 1, 2025
• Last Updated: July 24, 2023

Record last verified: 2023-07

Locations

NL (1)