A Trial on Different Dosages of Vitamin D in Preterm Infants With Late-onset Sepsis

Study Overview
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Brief Summary
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This is a randomized controlled trial (RCT) to evaluate the influence of different doses of vitamin D3 (800 IU/d versus 400 IU/d), on serum levels of interleukin (IL)-6, TNF-alpha and C- reactive (CRP) in premature infants with clinical evidence of late-onset sepsis and to assess its influence on clinical outcomes of these infants.

Detailed Description
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Vitamin D has an important role in the regulation of both the innate and adaptive immune systems. There are very few studies of such roles in the neonatal population. It is potentially an attractive therapeutic agent for sepsis given its low cost and low risk of toxicity and side effects. There is no consensus regarding to the dose of vitamin D supplementation required for preterm infants given the paucity of evidence. AAP and ESPGHAN have recommended different dosages of vitamin D ranging from 400 IU to 1000 IU per day. The influence of different doses of vitamin D on immunological status and clinical outcomes of preterm infants with late-onset sepsis has not been evaluated before. This RCT will evaluate the influence of different doses of vitamin D3 (800 IU/d versus 400 IU/d), on serum levels of interleukin (IL)-6, TNF-alpha and C- reactive (CRP) in premature infants with clinical evidence of late-onset sepsis we will also evaluate their safety and influence on clinical outcomes of these infants

Official Title
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Effect of Different Dosages Oral Vitamin D on Serum Interleukin-6 in Preterm Infants With Late-onset Sepsis

Conditions
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Prematurity, Late-onset Sepsis

Intervention / Treatment
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* Drug: High-dose vitamin D 3
* Drug: Conventional-Dose Vitamin D 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm Infants (28-37 wk gestational age) Late-onset sepsis defined as clinical signs suggestive of infection after 72 h of birth. Clinical sepsis will be defined as the presence of three or more of the following categories of clinical signs: Temperature instability (hypothermia, hyperthermia); Respiratory (grunting, intercoastal retraction, apnea, tachypnea, cyanosis); Neurologic (hypotonia, lethargy, seizures); Gastrointestinal (feeding intolerance, abdominal distension). Exclusion Criteria: Major congenital anomalies. Chromosomal anomalies. Known inborn error(s) of metabolism

Ages Eligible for Study
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Minimum Age: 3 Days
Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-dose vitamin D<br>Will receive oral cholecalciferol (vitamin D3) in a single daily dose of 800 IU from the time of diagnosis of sepsis until discharge from the NICU | Drug: High-dose vitamin D 3<br>* Will receive oral cholecalciferol (vitamin D3) in a single daily dose of 800 IU from the time of diagnosis of sepsis until discharge from the NICU<br>* Other names: High-dose cholecalciferol;|
| Active Comparator: Conventional-dose vitamin D<br>Will receive oral cholecalciferol (vitamin D3) in a single daily dose of 400 IU from the time of diagnosis of sepsis until discharge from the NICU | Drug: Conventional-Dose Vitamin D 3<br>* Will receive oral cholecalciferol (vitamin D3) in a single daily dose of 400 IU from the time of diagnosis of sepsis until discharge from the NICU<br>* Other names: Conventional-dose cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum interleukin-6 | Serum levels of interleukin-6 (IL-6) will be evaluated at enrollment and 7 days after daily vitamin D supplementation therapy. IL-6 concentrations will be determined by Endogenous Interleukin-ELISA | At trial entry and 7 days after daily vitamin D supplementation therapy | 
| Serum tumor necrosis-alpha | Serum levels of tumor necrosis-alpha (TNF-alpha) will be evaluated at enrollment and 7 days after daily vitamin D supplementation therapy | At trial entry and 7 days after daily vitamin D supplementation therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum C-reactive protein (CRP) | Serum CRP will be evaluated at enrollment and 7 days | At trial entery and 7 days after daily vitamin D supplementation therapy | 
| Serum 25(OH)D levels | Serum 25(OH)D levels will be measured by ELISA at trial entry, at day 7 and at 40 weeks postmenstrual age | at trial entry, 7 days after daily vitamin D supplementation therapy and at 40 weeks postmenstrual age | 
| Serum calcium, phosphorus and urinary calcium | Participants will be followed for the duration of hospital stay, serum calcium, phosphorus and urinary calcium well be assessed every week for an expected average of 5 weeks | Participants will be followed for the duration of hospital stay, serum calcium, phosphorus and urinary calcium well be assessed every week for an expected average of 5 weeks | 
| Abdominal ultrasonography | Abdominal ultrasonography to detect any nephrocalcinosis will be done at 40 weeks postmenstrual age | 40 weeks postmenstrual age | 
| Mortality | In-hospital mortality during NICU admission for an expected average of 5 weeks | Baseline | 
| Neonatal morbidities | Participants will be followed for the duration of hospital stay, for an expected average of 5 weeks and the incidence of neonatal morbidities e.g. NEC, retinopathy of prematurity, disseminated intravascular coagulopathy and renal dysfunction will be assessed | Participants will be followed for the duration of hospital stay, for an expected average of 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, late-onset sepsis, Preterm, Dose, Interleukin-6, Tumor necrosis factor-alpha