Clinical trial NCT04041765: IgM-Enriched Immunoglobulin for Neonatal Sepsis
Official title: Efficacy of Prophylactic IgM-Enriched Immunoglobulin for the Management of Early-Onset Neonatal Sepsis in Very Low Birth Weight Preterm Neonates; A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Neonatal Sepsis, Early-Onset
Very Low Birth Weight Infant
Inflammation
Infant, Newborn, Disease
Keywords: IgM-enriched Intravenous Immunoglobulin
Lead sponsor: Fakultas Kedokteran Universitas Indonesia
Sponsor class: OTHER
First posted: 2019-08-01
Enrollment: 70
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study compares giving prophylactic IgM enriched Intravenous Immunoglobulin (IVIG) with placebo in 1 hour after birth, in neonates with risk factors of Early-Onset Neonatal Sepsis (EONS). In addition to the intervention, standard regimen antibiotics are also given within 1 hour. The IVIG is given for 3 days and primary and secondary outcomes will be collected. Risk factors are both from maternal and neonate origin.

Detailed description: This randomized-controlled trial conducted in Cipto Mangunkusumo Hospital, Jakarta, Indonesia aims to determine the efficacy of prophylactic IgM-Enriched IVIG in preventing EONS. A total of 70 very low birth weight (VLBW) neonates with risk factors for EONS including maternal factors of premature rupture of membrane (PROM), fever, urinary tract infection (UTI), chorioamnionitis, and neonatal factor of prematurity and resuscitation history will be collected. These neonates within 1 hour of life will then be administered either placebo or IgM-enriched IVIG 0.25g/kg/day for 3 days, in addition to first-line empiric antibiotic. Randomization is done using simple randomization. Triple masking (Participant, Investigator, Outcomes Assessor) is conducted.

These neonates will then be clinically observed and evaluated for early mortality (mortality below 7 days), hemodynamics, length of stay, blood culture results, C-Reactive Protein (CRP), IT ratio, routine hematological examination, and IgGAME as parameters of improvement and prevention of EONS.

STATA version 12 (Macintosh version) will be used for data management and statistical analyses. The variables will first be presented descriptively, continued with bivariate and multivariate analysis. Bivariate analysis will be conducted between independent and dependent variables using chi-square/Fisher's exact test, Student's t-test, and Kruskal-Wallis. Variables with p-values \<0.25 will be included in the multivariate analysis using logistic regression. The investigators will use two-sided p-values in our analysis with a p \< 0.05 level of significance.

Eligibility criteria: Inclusion Criteria:

* Very low birth weight infants (\< 1500 g)
* Gestational age below 32 weeks
* Risk of Early-Onset sepsis from maternal and neonate factors
* Inborn neonates

Exclusion Criteria:

* Birth weight \< 600 g
* Gestational age \< 26 weeks
* Multiple Congenital Anomaly
* Neonates with suspected congenital syndrome

Primary outcomes:
measure: Early Mortality Rate
timeFrame: 1 week
Secondary outcomes:
measure: Positive blood culture
timeFrame: 1 week
measure: Duration of NICU stay
timeFrame: Through study completion, an average of 3 months
measure: Quantitative CRP Levels
timeFrame: 1 week
measure: IT Ratio value
timeFrame: 1 week
measure: Leukocyte count
timeFrame: 1 week
measure: IgGAME (IgG, IgM, IgA, IgE) Levels
timeFrame: 1 week
Other outcomes:
Locations:
Study officials:
affiliation: Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital
name: Rinawati Rohsiswatmo, MD, PhD
role: STUDY_CHAIR
affiliation: Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital
name: Nina D Putri, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Capasso L, Borrelli AC, Parrella C, Lama S, Ferrara T, Coppola C, Catania MR, Iula VD, Raimondi F. Are IgM-enriched immunoglobulins an effective adjuvant in septic VLBW infants? Ital J Pediatr. 2013 Oct 7;39:63. doi: 10.1186/1824-7288-39-63.
citation: Haque KN, Zaidi MH, Bahakim H. IgM-enriched intravenous immunoglobulin therapy in neonatal sepsis. Am J Dis Child. 1988 Dec;142(12):1293-6. doi: 10.1001/archpedi.1988.02150120047038.
citation: Reith HB, Rauchschwalbe SK, Mittelkotter U, Engemann R, Thiede A, Arnold A, Lissner R. IgM-enriched immunoglobulin (pentaglobin) positively influences the course of post-surgical intra-abdominal infections. Eur J Med Res. 2004 Oct 29;9(10):479-84.
citation: Capasso L, Borrelli AC, Pirozzi MR, Bucci L, Albachiara R, Ferrara T, Raimondi F. IgM and IgA enriched polyclonal immunoglobulins reduce short term mortality in extremely low birth weight infants with sepsis: a retrospective cohort study. Minerva Pediatr (Torino). 2021 Feb;73(1):3-7. doi: 10.23736/S2724-5276.18.04850-8. Epub 2018 Feb 19.
citation: Capasso L, Borrelli AC, Ferrara T, Coppola C, Cerullo J, Izzo F, Caiazza R, Lama S, Raimondi F. Immunoglobulins in neonatal sepsis: has the final word been said? Early Hum Dev. 2014 Sep;90 Suppl 2:S47-9. doi: 10.1016/S0378-3782(14)50013-8.