Vitamin D Supplementation for Extremely Preterm Infants

Phase 2

Completed

• Conditions: Vitamin D Deficiency; Preterm Infants; Bronchopulmonary Dysplasia
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Cholecalciferol

• Registration Number: NCT01600430
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

The study hypothesis states that giving early enteral Vitamin D supplementation to preterm infants will decrease respiratory morbidity in extremely preterm infants.

Detailed Description

After informed consent obtained, infants will be randomized using computer-generated stratified randomization codes by the pharmacy. Clinicians, researcher, and primary caregivers will be masked. Subjects will be randomly assigned to one of the treatment arms or to a placebo concurrent control.

Early vitamin D supplementation/placebo will be initiated within the first 7 days after birth. Premature infants will be randomized to receive one of the 3 fixed doses of vitamin D: either placebo (zero dose), 200 IU/day, or 800 IU/day. The supplementation will be started within 72 hours of enteral feeds being initiated and will continue until postnatal day 28. After this period of supplementation, routine supplementation will be conducted in all groups.

Remnant cord blood samples will be analyzed for vitamin D levels (serum hydroxyvitamin D \[25(OH)D\]. Two circulating vitamin D concentrations (25(OH)D concentrations) will be measured on postnatal days 14 and 28. Urine samples will be collected weekly, to determine calcium excretion if high serum calcium concentrations are found.

Supplementation will be discontinued and infant will exit the study if surgical necrotizing enterocolitis/bowel perforation is diagnosed, if 25 (OH)D concentrations \>60ng/mL (\>150nmol/L; potentially toxic) are detected or, if infant NPO for greater than 24 hours. If infant made briefly NPO (\<24h) for feeding intolerance, suspected sepsis, hypotension,hemodynamically significant PDA, or respiratory difficulties, enteral vitamin D will not be discontinued.

All infants will be followed to discharge for primary, secondary outcomes as well as adverse events.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-05-14
• Study First Submitted QC: 2012-05-15
• Study First Posted: 2012-05-17
• Study Start: 2012-06
• Primary Completion: 2014-12
• Study Completion: 2016-12
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-08
• Last Update Posted: 2017-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Infants admitted to the Regional Newborn ICU of the University of Alabama with gestational age between 23-27 completed weeks

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Exclusion Criteria

• Major congenital/chromosomal anomalies
• Moribund infant with low likelihood of survival, in opinion of the clinical team

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Identical-appearing treatment that does not contain the test drug given orally four times per day.
Oral Vitamin D--200 IU/day	Cholecalciferol	Cholecalciferol 200 IU given orally once per day
Oral Vitamin D--800 IU/day	Cholecalciferol	Cholecalciferol 800 IU given orally once per day

Primary Outcome Measures

Name	Time	Method
Serum vitamin D concentration	Day after birth 28	Serum vitamin D levels determined by enzyme immunoassay obtained from whole blood (remnant sample or obtained during clinical blood draw)
Total number of days alive and off respiratory support in the first 28 days	28 days	The total number of days alive and off respiratory support. Respiratory support is defined as need of supplemental oxygen and/or positive pressure ventilation to maintain normal target oxygen saturations (88-95%).

Secondary Outcome Measures

Name	Time	Method
Death	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Cardiorespiratory failure
Sepsis	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Culture proven or culture negative clinically treated course consistent with sepsis
Duration of mechanical ventilation after randomization	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Counted as number of days on which an infant is on mechanical ventilation for any part of a calendar day
Need for supplemental oxygen at 36 weeks of corrected age (Physiologic definition)	36 weeks gestational age corrected	A physiologic oxygen challenge test will be administered to infants from 36.0 weeks gestation to 37.0 weeks gestation to determine a need for supplemental oxygen to keep saturation levels between 88-95%.
Urine calcium level	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Calcium measurement per urine, random sampling. High level (\>95%tile) urine calcium to creatinine ratio is \>3.8 mmol/mmol.
Number of sepsis episodes treated with antibiotics for at least 5 days	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Number of episodes of culture proven or clinically suspected sepsis episodes treated with antibiotics for at least 5 days
Days alive and off mechanical ventilation in the first 28 days after birth	28 days	Counted as days alive without mechanical ventilation for any part of a day
Surgical necrotizing enterocolitis or intestinal perforation	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Radiographic documentation of pneumatosis or intestinal perforation or treatment course for clinical necrotizing enterocolitis per Bell's stage greater than 1.
Number of re-intubation events	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Counted as number of reintubations for purposes of respiratory support
25(OH)D concentrations >60ng/ml (150 nmol/L)	28 days postnatal age (+/- 3 days)	Vitamin D measurement per blood obtained either centrally or by heel stick.
Serum calcium level	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Serum calcium measurement per blood obtained either centrally or by heel stick, performed for clinical care. High serum calcium level is greater than 3 mmol/l of total calcium or total calcium of \>12 mg/dL, or ionized calcium \>2 mml/L.
Meningitis	Participants will be followed for the duration of hospital stay, an expected average of 4 months	Culture proven or culture negative clinically treated course consistent with meningitis

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States