IgM-Enriched Immunoglobulin for Neonatal Sepsis

Inflammation Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04041765
• Other study ID #: 19-11-432
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: September 2019
• Est. completion date: August 2020

Study information

• Verified date: July 2019
• Source: Fakultas Kedokteran Universitas Indonesia
• Contact: Rinawati Rohsiswatmo, MD, PhD
• Phone: +62811133094
• Email: rinarohsis[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: August 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Hour

Eligibility

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

Related Conditions & MeSH terms

• Birth Weight
• Infant, Newborn, Disease
• Infant, Newborn, Diseases
• Inflammation
• Neonatal Sepsis
• Neonatal Sepsis, Early-Onset
• Sepsis
• Toxemia
• Very Low Birth Weight Infant

Intervention

Drug:
• IgM-enriched IVIG
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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fakultas Kedokteran Universitas Indonesia

References & Publications (5)

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. Review. — View 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. — View 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 (ELBW) with sepsis: a retrospective cohort study. Minerva Pediatr. 2018 Feb 19. doi: 10.23736/S0026-4946.18.04850-8. [Epub ahead of print] — View 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. — View Citation

Reith HB, Rauchschwalbe SK, Mittelkötter 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early Mortality Rate	Neonates in the treatment group should have lower mortality rate in the first week of life	1 week
Secondary	Positive blood culture	Neonates in the treatment group should have less number of positive blood culture than those in the place group	1 week
Secondary	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
Secondary	Quantitative CRP Levels	Neonates in the treatment group should have lower CRP levels than those in the placebo group	1 week
Secondary	IT Ratio value	Neonates in the treatment group should have lower IT Ratio value than those in the placebo group	1 week
Secondary	Leukocyte count	Neonates in the treatment group should have lower Leukocyte count than those in the placebo group	1 week
Secondary	IgGAME (IgG, IgM, IgA, IgE) Levels	Neonates in the treatment group should have higher IgGAME levels than those in the placebo group	1 week