IgM-Enriched Immunoglobulin for Neonatal Sepsis
Primary Purpose
Neonatal Sepsis, Early-Onset, Very Low Birth Weight Infant, Inflammation
Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
IgM-enriched IVIG
Sponsored by
About this trial
This is an interventional prevention trial for Neonatal Sepsis, Early-Onset focused on measuring IgM-enriched Intravenous Immunoglobulin
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment Group
Placebo Group
Arm Description
IgM-enriched IVIG given with dose of 0.25g/kg over 3 hours for 3 days in addition to Antibiotics
Antibiotics only
Outcomes
Primary Outcome Measures
Early Mortality Rate
Neonates in the treatment group should have lower mortality rate in the first week of life
Secondary Outcome Measures
Positive blood culture
Neonates in the treatment group should have less number of positive blood culture than those in the place group
Duration of NICU stay
Neonates in the treatment group should be discharged earlier than those in the placebo group
Quantitative CRP Levels
Neonates in the treatment group should have lower CRP levels than those in the placebo group
IT Ratio value
Neonates in the treatment group should have lower IT Ratio value than those in the placebo group
Leukocyte count
Neonates in the treatment group should have lower Leukocyte count than those in the placebo group
IgGAME (IgG, IgM, IgA, IgE) Levels
Neonates in the treatment group should have higher IgGAME levels than those in the placebo group
Full Information
NCT ID
NCT04041765
First Posted
July 27, 2019
Last Updated
July 31, 2019
Sponsor
Fakultas Kedokteran Universitas Indonesia
1. Study Identification
Unique Protocol Identification Number
NCT04041765
Brief Title
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
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 2019 (Anticipated)
Primary Completion Date
June 2020 (Anticipated)
Study Completion Date
August 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fakultas Kedokteran Universitas Indonesia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neonatal Sepsis, Early-Onset, Very Low Birth Weight Infant, Inflammation, Infant, Newborn, Disease
Keywords
IgM-enriched Intravenous Immunoglobulin
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Group
Arm Type
Experimental
Arm Description
IgM-enriched IVIG given with dose of 0.25g/kg over 3 hours for 3 days in addition to Antibiotics
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
Antibiotics only
Intervention Type
Drug
Intervention Name(s)
IgM-enriched IVIG
Other Intervention Name(s)
Pentaglobin®
Intervention Description
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
Primary Outcome Measure Information:
Title
Early Mortality Rate
Description
Neonates in the treatment group should have lower mortality rate in the first week of life
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Positive blood culture
Description
Neonates in the treatment group should have less number of positive blood culture than those in the place group
Time Frame
1 week
Title
Duration of NICU stay
Description
Neonates in the treatment group should be discharged earlier than those in the placebo group
Time Frame
Through study completion, an average of 3 months
Title
Quantitative CRP Levels
Description
Neonates in the treatment group should have lower CRP levels than those in the placebo group
Time Frame
1 week
Title
IT Ratio value
Description
Neonates in the treatment group should have lower IT Ratio value than those in the placebo group
Time Frame
1 week
Title
Leukocyte count
Description
Neonates in the treatment group should have lower Leukocyte count than those in the placebo group
Time Frame
1 week
Title
IgGAME (IgG, IgM, IgA, IgE) Levels
Description
Neonates in the treatment group should have higher IgGAME levels than those in the placebo group
Time Frame
1 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Minute
Maximum Age & Unit of Time
1 Hour
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rinawati Rohsiswatmo, MD, PhD
Phone
+62811133094
Email
rinarohsis@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rinawati Rohsiswatmo, MD, PhD
Organizational Affiliation
Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Nina D Putri, MD, PhD
Organizational Affiliation
Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24098953
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.
Results Reference
background
PubMed Identifier
3195529
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.
Results Reference
background
PubMed Identifier
15546815
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.
Results Reference
background
PubMed Identifier
29460549
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.
Results Reference
background
PubMed Identifier
25220128
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.
Results Reference
background
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IgM-Enriched Immunoglobulin for Neonatal Sepsis
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