IgM-Enriched Immunoglobulin for Neonatal Sepsis

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Neonatal Sepsis, Early-Onset, Very Low Birth Weight Infant, Inflammation, Infant, Newborn, Disease

Intervention / Treatment
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* Drug: IgM-enriched IVIG


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 1 Hour

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>IgM-enriched IVIG given with dose of 0.25g/kg over 3 hours for 3 days in addition to Antibiotics | Drug: IgM-enriched IVIG<br>* Contains human plasma protein 50mg/ml. With composition of Immunoglobulin M (IgM) 6mg, Immunoglobulin A (IgA) 6mg, Immunoglobulin G (IgG) 38mg (IgG subcl. approx. 63 % IgG1, 26 % IgG2, 4 % IgG3 and 7 % IgG4), Glucose monohydrate, sodium chloride, water for injections<br>* Other names: Pentaglobin®;|
| Placebo Comparator: Placebo Group<br>Antibiotics only | Drug: IgM-enriched IVIG<br>* Contains human plasma protein 50mg/ml. With composition of Immunoglobulin M (IgM) 6mg, Immunoglobulin A (IgA) 6mg, Immunoglobulin G (IgG) 38mg (IgG subcl. approx. 63 % IgG1, 26 % IgG2, 4 % IgG3 and 7 % IgG4), Glucose monohydrate, sodium chloride, water for injections<br>* Other names: Pentaglobin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Mortality Rate | Neonates in the treatment group should have lower mortality rate in the first week of life | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive blood culture | Neonates in the treatment group should have less number of positive blood culture than those in the place group | 1 week | 
| Duration of NICU stay | Neonates in the treatment group should be discharged earlier than those in the placebo group | Through study completion, an average of 3 months | 
| Quantitative CRP Levels | Neonates in the treatment group should have lower CRP levels than those in the placebo group | 1 week | 
| IT Ratio value | Neonates in the treatment group should have lower IT Ratio value than those in the placebo group | 1 week | 
| Leukocyte count | Neonates in the treatment group should have lower Leukocyte count than those in the placebo group | 1 week | 
| IgGAME (IgG, IgM, IgA, IgE) Levels | Neonates in the treatment group should have higher IgGAME levels than those in the placebo group | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgM-enriched Intravenous Immunoglobulin