Neonatal Sepsis, Early-OnsetPhase 3NCT04041765
IgM-Enriched Immunoglobulin for Neonatal Sepsis
A Phase 3 study testing IgM-enriched IVIG in people with Neonatal Sepsis, Early-Onset and Very Low Birth Weight Infant, run by Fakultas Kedokteran Universitas Indonesia.
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. Read more about this study
- Who is it for?
- Ages 1 minute to 1 hour
- Conditions the study is for
- Neonatal Sepsis, Early-Onset, Very Low Birth Weight Infant, Inflammation
- What is being tested?
- IgM-enriched IVIG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- Sep 2019to Aug 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 minute to 1 hour
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Very low birth weight infants (< 1500 g)
- Gestational age below 32 weeks
- Risk of Early-Onset sepsis from maternal and neonate factors
- Inborn neonates
Who cannot join
- Birth weight < 600 g
- Gestational age < 26 weeks
- Multiple Congenital Anomaly
- Neonates with suspected congenital syndrome
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read the 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.
- Conditions
- Neonatal Sepsis, Early-Onset, Very Low Birth Weight Infant, Inflammation, Infant, Newborn, Disease
- Being tested
- IgM-enriched IVIG
- Keywords
- IgM-enriched Intravenous Immunoglobulin
- Medical subject headings
- Neonatal Sepsis, Inflammation, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IgM-enriched IVIGDrug
Also called Pentaglobin®
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
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Experimental | IgM-enriched IVIG given with dose of 0.25g/kg over 3 hours for 3 days in addition to Antibiotics Receives: Drug: IgM-enriched IVIG |
| Placebo Group | Placebo comparator | Antibiotics only Receives: Drug: IgM-enriched IVIG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Mortality Rate
Neonates in the treatment group should have lower mortality rate in the first week of life
Measured: 1 week
Secondary outcomes (6)
Positive blood culture
Neonates in the treatment group should have less number of positive blood culture than those in the place group
Measured: 1 week
Duration of NICU stay
Neonates in the treatment group should be discharged earlier than those in the placebo group
Measured: 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
Measured: 1 week
IT Ratio value
Neonates in the treatment group should have lower IT Ratio value than those in the placebo group
Measured: 1 week
Leukocyte count
Neonates in the treatment group should have lower Leukocyte count than those in the placebo group
Measured: 1 week
IgGAME (IgG, IgM, IgA, IgE) Levels
Neonates in the treatment group should have higher IgGAME levels than those in the placebo group
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study startSep 2019 (estimated)
- Primary completionJun 2020 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Neonatal Sepsis, Early-OnsetStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fakultas Kedokteran Universitas Indonesia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rinawati, Fakultas Kedokteran Universitas Indonesia
- Investigators
- Rinawati Rohsiswatmo, MD, PhD, Study chair, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo HospitalNina D Putri, MD, PhD, Principal investigator, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04041765
- Sponsor's protocol ID
- 19-11-432
- Status last verified
- Jul 2019
- First submitted
- 27 Jul 2019
- Last updated
- 1 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24098953Haque 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.
PubMed 3195529Reith 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.
PubMed 15546815Capasso 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.
PubMed 29460549Capasso 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.
PubMed 25220128
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04041765
- Acronym / sponsor ID
- 19-11-432
- Conditions
- Neonatal Sepsis, Early-Onset, Very Low Birth Weight Infant, Inflammation, Infant, Newborn, Disease
- Keywords
- IgM-enriched Intravenous Immunoglobulin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Fakultas Kedokteran Universitas IndonesiaUniversity, hospital or other
- Study start
- Sep 2019 (estimated)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 1 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Experimental | Drug: IgM-enriched IVIGIgM-enriched IVIG given with dose of 0.25g/kg over 3 hours for 3 days in addition to Antibiotics |
| Placebo Group | Placebo comparator | Drug: IgM-enriched IVIGAntibiotics only |
Who may qualify
- Ages
- 1 minute to 1 hour
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Very low birth weight infants (< 1500 g)
- Gestational age below 32 weeks
- Risk of Early-Onset sepsis from maternal and neonate factors
- Inborn neonates
Key exclusion criteria (4 listed)
- Birth weight < 600 g
- Gestational age < 26 weeks
- Multiple Congenital Anomaly
- Neonates with suspected congenital syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IgM-enriched IVIGAlso: Pentaglobin®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 | Drug | Placebo Group, Treatment Group |
Primary outcome
Early Mortality Rate
Time frame: 1 week
Neonates in the treatment group should have lower mortality rate in the first week of life
6 secondary outcomes
Positive blood culture
Time frame: 1 week
Duration of NICU stay
Time frame: Through study completion, an average of 3 months
Quantitative CRP Levels
Time frame: 1 week
IT Ratio value
Time frame: 1 week
Leukocyte count
Time frame: 1 week
IgGAME (IgG, IgM, IgA, IgE) Levels
Time frame: 1 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2019.
- Background: PubMed 24098953Capasso 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.
- Background: PubMed 3195529Haque 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.
- Background: PubMed 15546815Reith 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.
- Background: PubMed 29460549Capasso 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.
- Background: PubMed 25220128Capasso 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rinawati Rohsiswatmo, MD, PhD study chair
Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital
Nina D Putri, MD, PhD principal investigator
Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IgM-enriched IVIG in people with Neonatal Sepsis, Early-Onset and Very Low Birth Weight Infant, run by Fakultas Kedokteran Universitas Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rinawati Rohsiswatmo, MD, PhD (+62811133094, rinarohsis@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early Mortality Rate (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04041765, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2019; AzTrials last refreshed its copy on 30 Oct 2026.