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

The Effect of Vitamin D Administration on Sepsis Score and C-Reactive Protein Levels in Preterm Infants With Neonatal Sepsis

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.

Study Overview

• Status: Completed
• Conditions: Preterm Infants; Neonatal Sepsis
• Intervention / Treatment: Drug: Vitamin D; Drug: Vitamin D

Detailed Description

The target population in this study is preterm neonates diagnosed with sepsis. This is a multicenter study. The accessible population in this study is patients who are treated in the Neonatal High Care Unit (NHCU) and Neonatal Intensive Care Unit (NICU) at Dr. Hasan Sadikin General Hospital Bandung and Bandung Kiwari Hospital, who meet the inclusion criteria and do not meet the exclusion criteria, and whose parents or guardians are willing to participate in the study by signing the informed consent form.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Contacts and Locations

Study Locations

• Indonesia
  • West Java
    • Bandung, West Java, Indonesia, 40161
      • Hasan Sadikin General Hospital
    • Bandung, West Java, Indonesia, 40233
      • Rumah Sakit Umum Daerah Bandung Kiwari

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion criteria for the case group used in this study are neonates (aged 0-28 days or with a maximum postmenstrual age of 42 weeks) with a gestational age of 28-36 weeks who are treated in the Neonatal High Care Unit (NHCU) and Neonatal Intensive Care Unit (NICU) at Dr. Hasan Sadikin General Hospital, Bandung, and Bandung Kiwari Hospital, Bandung and who meet the following inclusion criteria:

1. 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.
2. Parents or legal guardians are willing to participate in the study and sign the informed consent form.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Antibiotics only; Group 1 consisted of subjects who were given only antibiotics due to medical conditions requiring fasting.
Active Comparator: Vitamin D 400 IU; 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 400 IU for 7 days; Other Names: L-VIT D3; Drug: Vitamin D; Vitamin D 800 IU for 7 days; Other Names: L-VIT D3
Active Comparator: Vitamin D 800 IU; 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; Vitamin D 400 IU for 7 days; Other Names: L-VIT D3; Drug: Vitamin D; Vitamin D 800 IU for 7 days; Other Names: L-VIT D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Fakultas Kedokteran Universitas Padjadjaran
• Investigators: Study Director: 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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2025
• Primary Completion (Actual): December 1, 2025
• Study Completion (Actual): December 8, 2025

Study Registration Dates

• First Submitted: September 22, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: adjuvant therapy; preterm infants; vitamin D; neonatal sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Neonatal Sepsis; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Secosteroids; Vitamin D
• Other Study ID Numbers: DP. 04.03/D.XIV.6.5/337/2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication
• IPD Sharing Time Frame: Beginning 3 months and ending 1 year after the publication of results
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No