A Panel of Biomarkers in Diagnosing Late-onset Neonatal Sepsis and Necrotizing Enterocolitis in Sibu Hospital (PISALONS)

This is a cross-sectional study to evaluate the utilities of a panel of biomarkers (Procalcitonin, Interleukin-6, Serum Amyloid A and Apolipoprotein C2) versus the gold standard blood culture result diagnosing late-onset neonatal sepsis (LONS) and/or necrotizing enterocolitis (NEC). Neonates who meet the initial screening criteria for suspected LONS or NEC will be recruited into the study. A group of 50 neonates who are clinically well, admitted to the nursery or general ward for reasons other than neonatal sepsis or NEC will also be recruited into the study.

Study Overview

• Status: Unknown
• Conditions: Necrotizing Enterocolitis; Neonatal SEPSIS
• Intervention / Treatment: Other: No intervention

Detailed Description

The diagnosis of neonatal sepsis is challenging especially the very low birth weight infants as the signs and symptoms of sepsis are nonspecific and can be attributed to non-infected aetiologies including exacerbation of bronchopulmonary dysplasia, apnoea of prematurity and gastroesophageal reflux. Blood culture remains the gold standard for diagnosing septicaemia (either bacteremia or fungemia). However, its effectiveness in the population of preterm infants is compromised.Given the dire consequences of not treating the sepsis early, clinicians tend to have a low threshold for treatment. This leads to overuse of antimicrobials, promotion of antimicrobial resistance, exposure of infants to avoidable side effects from the antimicrobial treatment, prolonged hospitalisation and increased healthcare costs. Hence, there is a need for a clearly defined algorithm for diagnosing LONS and NEC. This study aims to examine the diagnostic utilities of a panel of sepsis biomarkers and explore if they can be incorporated into a diagnostic algorithm which hopefully, can be translated into clinical practice in the future.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Shirin Hui Tan; Phone Number: +6082-276820; Email: shirin_hui88@yahoo.com

Study Locations

• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Sarawak General Hospital
      • Contact: Shirin H Tan; Phone Number: 6082276820; Email: shirin_hui88@yahoo.com
      • Sub-Investigator: Ann Cheng Wong
      • Sub-Investigator: Lee Gaik Chan
      • Sub-Investigator: Janet Lin Yee Hii
      • Sub-Investigator: Debbie Diewo
      • Sub-Investigator: Kim Lai Ng
      • Sub-Investigator: Janet Huey Jing Liew
      • Sub-Investigator: Hui Ling Sim
    • Sibu, Sarawak, Malaysia, 96000
      • Recruiting
      • Sibu Hospital
      • Contact: Shirin Hui Tan
      • Principal Investigator: See Chang Wong
      • Sub-Investigator: Teck Hock Toh
      • Sub-Investigator: Chae Hee Chieng
      • Sub-Investigator: Phaik Ngan Lee
      • Sub-Investigator: Yi-Pinn Tai
      • Sub-Investigator: Wei Nin Kong
      • Sub-Investigator: Justina Sie Wei Lau
      • Sub-Investigator: Hanizah Amran

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 1 month (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Neonates suspected of LONS and/or NEC admitted to the Neonatal Intensive Care Unit (NICU), Special Care Nursery (SCN) or Paediatric Medical 27 (PM27) wards in Sibu Hospital, Malaysia during the period of 1 July 2018 and 31 May 2020 will be screened for their eligibility. Apart from that, neonates admitted to Sibu Hospital for reasons other than neonatal sepsis or NEC will also be recruited into the study during the period of 1 June 2018 and 31 May 2020.

Description

Neonates with suspected LONS/NEC

Inclusion Criteria:

• Infants with signs and symptoms suggestive of sepsis and/or NEC and requiring full sepsis screening and start of intravenous antibiotic(s), or a change of antibiotics (if already on)
• Infants with postnatal age greater than 72 hours and less than 28 days of life, of all gestation
• Parents of potential neonates who are willing to give written informed consent

Healthy subjects

Inclusion Criteria:

• Clinically well infants admitted to Sibu Hospital for reasons other than neonatal sepsis or NEC
• Infants with postnatal age greater than 72 hours and less than 28 days of life, of all gestation

Exclusion Criteria:

• Infants who have lethal or life-threatening congenital abnormalities
• Infants who have chromosomal abnormalities
• Infants who have hypoxic ischemic encephalopathy
• Infants who are on steroid treatment
• Infants who received blood transfusions
• Post-operative infants

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Neonates with suspected LONS and/or NEC; A group of 150 neonates with suspected LONS and/or NEC will be recruited. No intervention will be given to the subjects. Blood sampling will be obtained from subjects at 4 time points (Hour 0, 24, 48 and 72) for analysis of the sepsis biomarkers of interest.	Other: No intervention; No intervention will be given to study subjects. Only blood will be obtained from study subjects.
Healthy neonates; A group of 50 neonates who are clinically well, admitted to the NICU for reasons other than neonatal sepsis or NEC will be recruited into the study to explore the kinetics and concentrations of the panel of biomarkers in healthy subjects comparing to subjects with suspected LONS/NEC. No intervention will be given to the subjects. Blood sampling will be obtained from subjects at 4 time points (Hour 0, 24, 48 and 72) for analysis of the sepsis biomarkers of interest.	Other: No intervention; No intervention will be given to study subjects. Only blood will be obtained from study subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic utilities of biomarkers of interest in diagnosing LONS	Diagnostic utilities of each individual biomarker (procalcitonin, interleukin-6, serum amyloid A and apolipoprotein C2) or in combination in diagnosing LONS	Hour 0 to 72
Diagnostic utilities of biomarkers of interest in diagnosing NEC	Diagnostic utilities of each individual biomarker (procalcitonin, interleukin-6, serum amyloid A and apolipoprotein C2) or in combination in diagnosing LONS	Hour 0 to 72

Collaborators and Investigators

• Sponsor: Clinical Research Centre, Malaysia
• Investigators: Principal Investigator: Shirin Hui Tan, Clinical Research Centre, Sarawak General Hospital, Malaysia

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2018
• Primary Completion (ANTICIPATED): May 31, 2021
• Study Completion (ANTICIPATED): August 31, 2021

Study Registration Dates

• First Submitted: June 25, 2018
• First Submitted That Met QC Criteria: June 25, 2018
• First Posted (ACTUAL): July 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Gastrointestinal Diseases; Infant, Newborn, Diseases; Gastroenteritis; Intestinal Diseases; Sepsis; Toxemia; Enterocolitis; Enterocolitis, Necrotizing; Neonatal Sepsis
• Other Study ID Numbers: NMRR-17-2491-38373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No