Effect of Vitamin D as Adjuvant Therapy in Preterm Infants With Neonatal Sepsis

NCT07245277 | Completed Phase 4 Results DMC

• 1 other identifier: DP. 04.03/D.XIV.6.5/337/2025
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn the effect of vitamin D as an adjunctive therapy for preterm neonates with sepsis measured by the outcomes, which are sepsis score and C-reactive protein after 7 days. The main questions it aims to answer are: Is there a difference in the results of the sepsis score (Modified Tollner Score and Sepsis Prediction Score) between groups of preterm neonates with sepsis who were given vitamin D as adjuvant therapy at doses of 400 IU/day, 800 IU/day, and those who were only given antibiotics? Is there a difference in CRP levels between groups of preterm neonates with sepsis who were given vitamin D as adjuvant therapy at doses of 400 IU/day, 800 IU/day, and those who were only given antibiotics? Participants will be divided into 3 groups: Group 1 consisted of subjects who were given only antibiotics due to medical conditions requiring fasting. Group 2 consisted of subjects who were able to receive enteral nutrition, were given antibiotics, and were supplemented with vitamin D3 at a dose of 400 IU once daily for 7 days. Group 3 consisted of subjects who were able to receive enteral nutrition, were given antibiotics, and were supplemented with vitamin D3 at a dose of 800 IU once daily for 7 days.

Conditions

Neonatal Sepsis; Preterm Infants

Keywords

adjuvant therapy; neonatal sepsis; preterm infants; vitamin D

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in the Modified Töllner Sepsis Scoring System After 7 Days

  Modified Töllner sepsis scoring system consists of clinical parameters including appearance, microcirculation, hypotonia, bradycardia/tachycardia, apnea of prematurity, respiratory distress, hepatomegaly, gastrointestinal symptoms, leucocyte count, Immature to Total Neutrophil (I/T) ratio, thrombocytopenia, C-reactive protein. Minimum value: 0 Maximum value: 26 Higher scores mean a worse outcome for neonatal sepsis

  Baseline (day-0) and at day-7

• Change From Baseline in the Sepsis Prediction Score After 7 Days

  Sepsis Prediction Score consists of clinical parameters including body temperature, decrease feeding volume/residuals, platelet counts, blood glucose changes, C-reactive protein, circulatory changes, increase of oxygen requirement, deterioration of respiratory function. Minimum value: 0 Maximum value: 8 Higher scores mean a worse outcome for neonatal sepsis

  Baseline (day-0) and at day-7

• Change From Baseline in the C-Reactive Protein Levels After 7 Days

  The blood sample was taken from the neonate to test for C-reactive protein (CRP) on day 0 and day 7. Minimum value: 0 Higher scores mean a worse outcome for neonatal sepsis

  Baseline (day-0) and at day-7

Study Arms (3)

Antibiotics only

NO INTERVENTION

Group 1 consisted of subjects who were given only antibiotics due to medical conditions requiring fasting.

Vitamin D 400 IU

ACTIVE COMPARATOR

Group 2 consisted of subjects who were able to receive enteral nutrition, were given antibiotics, and were supplemented with vitamin D3 at a dose of 400 IU once daily for 7 days.

Drug: Vitamin D

Vitamin D 800 IU

ACTIVE COMPARATOR

Group 3 consisted of subjects who were able to receive enteral nutrition, were given antibiotics, and were supplemented with vitamin D3 at a dose of 800 IU once daily for 7 days.

Drug: Vitamin D

Interventions

Vitamin D DRUG

Vitamin D 400 IU for 7 days

Also known as: L-VIT D3

Vitamin D 400 IU

Eligibility Criteria

• Age: 0 Days - 84 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients diagnosed with neonatal sepsis based on positive blood or cerebrospinal fluid cultures, or who meet the criteria for suspected sepsis with a Rodwell hematologic scoring system result of ≥3.
• Parents or legal guardians are willing to participate in the study and sign the informed consent form.

You may not qualify if:

• Patients with major congenital malformations such as anencephaly, encephalocele, holoprosencephaly, hydrocephalus, meningomyelocele, spina bifida, omphalocele, gastroschisis, or congenital heart disease.
• If during the 7-day monitoring period, a patient who was initially able to feed develops a medical condition requiring fasting (NPO).
• If during the 7-day monitoring period, a patient who initially had a medical condition requiring fasting is later able to feed again.

Sponsors & Collaborators

• Universitas Padjadjaran: lead

Study Sites (2)

Hasan Sadikin General Hospital

Bandung, West Java, 40161, Indonesia

Location

Rumah Sakit Umum Daerah Bandung Kiwari

Bandung, West Java, 40233, Indonesia

Location

Related Publications (4)

• Fort P, Salas AA, Nicola T, Craig CM, Carlo WA, Ambalavanan N. A Comparison of 3 Vitamin D Dosing Regimens in Extremely Preterm Infants: A Randomized Controlled Trial. J Pediatr. 2016 Jul;174:132-138.e1. doi: 10.1016/j.jpeds.2016.03.028. Epub 2016 Apr 11.

  PMID: 27079965 BACKGROUND

• Kamsiah K, Hasibuan BS, Arto KS. The relationship between vitamin D levels and clinical outcomes of neonatal sepsis in Haji Adam Malik Hospital Medan, Indonesia. Open Access Maced J Med Sci. 2021;9(B):698-703.

  BACKGROUND

• Cetinkaya M, Cekmez F, Buyukkale G, Erener-Ercan T, Demir F, Tunc T, Aydin FN, Aydemir G. Lower vitamin D levels are associated with increased risk of early-onset neonatal sepsis in term infants. J Perinatol. 2015 Jan;35(1):39-45. doi: 10.1038/jp.2014.146. Epub 2014 Aug 7.

  PMID: 25102323 BACKGROUND

• Hagag AA, El Frargy MS, Houdeeb HA. Therapeutic Value of Vitamin D as an Adjuvant Therapy in Neonates with Sepsis. Infect Disord Drug Targets. 2020;20(4):440-447. doi: 10.2174/1871526519666190626141859.

  PMID: 31241441 BACKGROUND

MeSH Terms

Conditions

Neonatal Sepsis

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Baseline difference: the control group (antibiotic only) consisted solely of neonates kept NPO (nil per os) for medical necessity. In contrast, the intervention groups (vitamin D 400 and 800 IU) were required to be on enteral nutrition. Repeated CRP testing was performed on day 7, although serial monitoring on day 3 is considered ideal. This constraint was due to limitations in blood sampling and laboratory resources at our hospital.

Results Point of Contact

• Title: Michelle Angelica Wijaya
• Organization: Universitas Padjadjaran

michelle13002@mail.unpad.ac.id

6281313996911

Study Officials

• Reni Ghrahani, MD, Ph.D

  Child Health Department Hasan Sadikin General Hospital Universitas Padjadjaran

  STUDY DIRECTOR

• Fiva A Kadi, MD, Ph.D

  Child Health Department Hasan Sadikin General Hospital Universitas Padjadjaran

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: November 24, 2025
• Study Start: August 2, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 8, 2025
• Last Updated: February 5, 2026
• Results First Posted: February 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Beginning 3 months and ending 1 year after the publication of results
• Access Criteria: A proposal that describes planned analyses must be submitted and a data sharing agreement must be signed. The proposal must be submitted to the principal investigator's email. The statistical methods for analyses of the proposal must be approved by independent review.

Locations

ID (2)