ViDES Trial (Vitamin D Extra Supplementation)

Study Overview
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Brief Summary
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The objective of the study is to compare supplementation with vitamin D at 800 IU/day to usual care for the first 28 days after birth with respect to 25 (OH) vitamin D levels and indicators of likely or plausible effects of vitamin D supplementation on the function or structure of the lung, bones, immune system, and brain in extremely premature (EP) infants who are <28 weeks gestational age (GA) or <1000 grams of birth weight (BW). The study results will be analyzed as intention to treat Bayesian analyses (Frequentist analyses will also be performed).

Official Title
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Randomized Trial of Enteral Vitamin D Supplementation in Infants < 28 Weeks Gestational Age or <1000 Grams Birth Weight

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: 800 IU/day vitamin D supplementation with feedings in the first 28 days after birth
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants born at < 28 weeks gestational age (GA) or <1000 grams birth weight (BW) Inborn Informed written consent in an Institutional Review Board (IRB)-approved manner Exclusion Criteria: GA >32 weeks regardless of birth weight (BW) Any major congenital anomaly A known congenital nonbacterial infection Prenatal diagnosis of disorders that affect vitamin D absorption (e.g, cystic fibrosis) Such severe illness or immaturity that the attending neonatologist judges intensive care to be unjustified.

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 96 Hours

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual care plus placebo<br>Infants will receive placebo (normal saline) in the first 28 days after birth. Care will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. When the infant receives about 120 to 160 mL/kg/day of fortified milk at 24 kcal/ounce, the infant will receive supplementation with 400 IU/day of vitamin D as usual care. | Dietary Supplement: Placebo<br>* Placebo is normal saline, given in the first 28 days after birth, prepared to have the same volume and appearance as vitamin D, which is a clear odorless solution.<br>* Other names: Normal saline;Other: Usual Care<br>* Care will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. When the infant receives about 120 to 160 mL/kg/day of fortified milk at 24 kcal/ounce, the infant will receive supplementation with 400 IU/day of vitamin D as usual care.<br>|
| Experimental: Usual care plus vitamin D supplementation<br>Infants will receive cholecalciferol 800 IU/day in the first 28 days after birth, given enterally four times per day (0.5mL per dose = 200 IU) until the infant is provided 400 IU/day (when feedings reach about 120 -160 mL/kg/day). At that point the study cholecalciferol will be reduced to 400 IU/day for a total supplementation of 800 IU/day. | Dietary Supplement: 800 IU/day vitamin D supplementation with feedings in the first 28 days after birth<br>* 800 IU/day Vitamin D supplementation until 400 IU/day are provided as part of usual care (started when infants receive full feedings of about 120-160 mL/kg/day). At that point the intervention becomes a supplement of 400 IU/day above that given with usual care. In this way all infants in the intervention group receive 800 IU/day of vitamin D total supplementation in the first 28 days after birth with feedings.<br>* Other names: Cholecalciferol;Other: Usual Care<br>* Care will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. When the infant receives about 120 to 160 mL/kg/day of fortified milk at 24 kcal/ounce, the infant will receive supplementation with 400 IU/day of vitamin D as usual care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25-hydroxyvitamin D (25[OH]D) level |  | about 28 days after birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25-hydroxyvitamin D (25[OH]D) level |  | 36 weeks after birth | 
| Type of respiratory support required at 36 weeks postmenstrual age | Data will be reported categorically as: Number of participants who survive without respiratory support Number of participants who survive with nasal cannula at ≤ 2 liters (L)/minute Number of participants who survive with nasal cannula >2 L/minute or noninvasive positive airway pressure Number of participants who survive with invasive mechanical ventilation Number of participants who die | 36 weeks postmenstrual age (or at the time of discharge home if earlier) | 
| Length of Hospital stay |  | from time of birth to time of discharge (about 0 to 60 weeks after birth) | 
| Number of participants who are still on respiratory support | Respiratory support includes supplemental oxygen and positive pressure ventilation. | 22 to 26 months corrected age | 
| Number of days of supplemental oxygen |  | from time of birth to time of discharge (about 0 to 60 weeks after birth) | 
| Number of days of mechanical ventilation |  | from time of birth to time of discharge (about 0 to 60 weeks after birth) | 
| Number of days of positive pressure support |  | from time of birth to time of discharge (about 0 to 60 weeks after birth) | 
| Number of participants who receive steroid treatment to decrease respiratory support |  | from baseline to 36 weeks postmenstrual age | 
| Number of participants with pulmonary hypertension |  | 36 weeks postmenstrual age | 
| Number of participants with wheezing |  | 2 years | 
| Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 28 days of life | 
| Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 36 weeks postmenstrual age | 
| Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 2 years | 
| Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 28 days of life | 
| Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 36 weeks postmenstrual age | 
| Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 2 years | 
| Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 28 days of life | 
| Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 36 weeks postmenstrual age | 
| Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. | 2 years | 
| Number of participants with any fractures |  | from baseline to 36 weeks postmenstrual age | 
| Number of participants with hospital-acquired sepsis |  | from day 3 after birth to the time of discharge (which is 0 to 60 weeks after birth) | 
| Calcium level |  | 0 to 36 weeks postmenstrual age | 
| Phosphorus level |  | 0 to 36 weeks postmenstrual age | 
| Alkaline phosphatase level |  | 0 to 36 weeks postmenstrual age | 
| Neurodevelopment as assessed by the Bayley-IV Scales of Infant and Toddler Development | Score ranges from 40 to 160, with a higher score indicating a better outcome. | 2 years | 
| Number of participants with neurodevelopmental impairment (NDI) |  | 2 years | 
| Number of participants who die or have a morbidity | Morbidities include retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), neurodevelopmental impairment (NDI), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA). | 36 weeks postmenstrual age | 
| Vitamin D status as indicated by serum concentration of 24,25(OH)2D3 as assessed by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) |  | about 28 days after birth | 
| Vitamin D status as indicated by serum concentration of 24,25(OH)2D3 as assessed by LC-MS/MS |  | 36 weeks postmenstrual age | 
| Vitamin D status as indicated by serum concentration of 3-epi-25(OH)D3 as assessed by LC-MS/MS |  | about 28 days after birth | 
| Vitamin D status as indicated by serum concentration of 3-epi-25(OH)D3 as assessed by LC-MS/MS |  | 36 weeks postmenstrual age | 
| Vitamin D status as indicated by serum concentration of 25(OH)D3 as assessed by LC-MS/MS |  | about 28 days after birth | 
| Vitamin D status as indicated by serum concentration of 25(OH)D3 as assessed by LC-MS/MS |  | 36 weeks postmenstrual age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premature infant, Vitamin D