Trial Outcomes & Findings for Prevention of Vitamin D Deficiency Following Pediatric CHD Surgery: a Phase II Dose Evaluation Randomized Controlled Trial Comparing Usual Care With a High Dose Pre-operative Supplementation Regimen Based on the Institute of Medicine Daily Upper Tolerable Intake Level (NCT NCT01838447)
NCT ID: NCT01838447
Last Updated: 2019-07-22
Results Overview
Blood 25OHD will be measured to determine vitamin D deficiency, with a concentration below 50 nmol/L used to define deficiency. A PICU admission blood sample could not be obtained for one patient in the Usual Care Group and one patient in the High Dose Group, thus the total number analyzed differs from the full sample size.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
46 participants
Primary outcome timeframe
1 day (On admission to the pediatric intensive care unit (PICU) following CHD surgery)
Results posted on
2019-07-22
Participant Flow
Participant milestones
| Measure |
Usual Care Group
This group will receive daily cholecalciferol (vitamin D3) based on the Adequate Intake (AI) for infants and the Recommended Dietary Allowance (RDA) for children over 1 year. Specific dose amounts are 400 IU per day for infants (0-1 year), and 600 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a placebo solution.
|
High Dose Group
This group will receive cholecalciferol (vitamin D3) based on the age-specific tolerable daily upper intake level (UL). Specific dose amounts are 1600 IU per day for infants (0-1 year), and 2400 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a dose of 1200 IU per day to account for vitamin D in formula.
Cholecalciferol: The High Dose group is based on the age-specific UL. These doses were chosen to elevate 25OHD well above 50 nmol/L, while minimizing the risk of vitamin D toxicity (e.g. hypercalcemia, hypercalciuria)
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
24
|
|
Overall Study
COMPLETED
|
20
|
21
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Usual Care Group
This group will receive daily cholecalciferol (vitamin D3) based on the Adequate Intake (AI) for infants and the Recommended Dietary Allowance (RDA) for children over 1 year. Specific dose amounts are 400 IU per day for infants (0-1 year), and 600 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a placebo solution.
|
High Dose Group
This group will receive cholecalciferol (vitamin D3) based on the age-specific tolerable daily upper intake level (UL). Specific dose amounts are 1600 IU per day for infants (0-1 year), and 2400 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a dose of 1200 IU per day to account for vitamin D in formula.
Cholecalciferol: The High Dose group is based on the age-specific UL. These doses were chosen to elevate 25OHD well above 50 nmol/L, while minimizing the risk of vitamin D toxicity (e.g. hypercalcemia, hypercalciuria)
|
|---|---|---|
|
Overall Study
Change in surgical plan
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Type of feeding is described for the sub-set of study participants who were \<1 year of age at the time of randomization
Baseline characteristics by cohort
| Measure |
Usual Care Group
n=20 Participants
This group will receive daily cholecalciferol (vitamin D3) based on the Adequate Intake (AI) for infants and the Recommended Dietary Allowance (RDA) for children over 1 year. Specific dose amounts are 400 IU per day for infants (0-1 year), and 600 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a placebo solution.
|
High Dose Group
n=21 Participants
This group will receive cholecalciferol (vitamin D3) based on the age-specific tolerable daily upper intake level (UL). Specific dose amounts are 1600 IU per day for infants (0-1 year), and 2400 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a dose of 1200 IU per day to account for vitamin D in formula.
Cholecalciferol: The High Dose group is based on the age-specific UL. These doses were chosen to elevate 25OHD well above 50 nmol/L, while minimizing the risk of vitamin D toxicity (e.g. hypercalcemia, hypercalciuria)
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
3.8 Months
n=20 Participants
|
4.6 Months
n=21 Participants
|
4.3 Months
n=41 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=20 Participants
|
11 Participants
n=21 Participants
|
18 Participants
n=41 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=20 Participants
|
10 Participants
n=21 Participants
|
23 Participants
n=41 Participants
|
|
Weight (kg)
|
5.8 kilograms
n=20 Participants
|
5.4 kilograms
n=21 Participants
|
5.7 kilograms
n=41 Participants
|
|
RACHS Score
|
3 units on a scale
n=20 Participants
|
2 units on a scale
n=21 Participants
|
3 units on a scale
n=41 Participants
|
|
Other active medical condition
|
7 Participants
n=20 Participants
|
7 Participants
n=21 Participants
|
14 Participants
n=41 Participants
|
|
Surgery season
Winter
|
5 Participants
n=20 Participants
|
6 Participants
n=21 Participants
|
11 Participants
n=41 Participants
|
|
Surgery season
Spring
|
2 Participants
n=20 Participants
|
3 Participants
n=21 Participants
|
5 Participants
n=41 Participants
|
|
Surgery season
Summer
|
8 Participants
n=20 Participants
|
6 Participants
n=21 Participants
|
14 Participants
n=41 Participants
|
|
Surgery season
Fall
|
5 Participants
n=20 Participants
|
6 Participants
n=21 Participants
|
11 Participants
n=41 Participants
|
|
Ethnicity
Caucasian
|
14 Participants
n=20 Participants
|
14 Participants
n=21 Participants
|
28 Participants
n=41 Participants
|
|
Ethnicity
Aboriginal
|
1 Participants
n=20 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=41 Participants
|
|
Ethnicity
Oriental
|
3 Participants
n=20 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=41 Participants
|
|
Ethnicity
African/West Indian
|
1 Participants
n=20 Participants
|
2 Participants
n=21 Participants
|
3 Participants
n=41 Participants
|
|
Ethnicity
Unknown/Other
|
1 Participants
n=20 Participants
|
4 Participants
n=21 Participants
|
5 Participants
n=41 Participants
|
|
Expected Duration to Surgery at Time of Enrolment
<2 months
|
18 Participants
n=20 Participants
|
18 Participants
n=21 Participants
|
36 Participants
n=41 Participants
|
|
Expected Duration to Surgery at Time of Enrolment
>2 months
|
2 Participants
n=20 Participants
|
3 Participants
n=21 Participants
|
5 Participants
n=41 Participants
|
|
Type of Feeding in Children <1 year
Breast fed
|
9 Participants
n=12 Participants • Type of feeding is described for the sub-set of study participants who were \<1 year of age at the time of randomization
|
10 Participants
n=12 Participants • Type of feeding is described for the sub-set of study participants who were \<1 year of age at the time of randomization
|
19 Participants
n=24 Participants • Type of feeding is described for the sub-set of study participants who were \<1 year of age at the time of randomization
|
|
Type of Feeding in Children <1 year
Formula fed
|
3 Participants
n=12 Participants • Type of feeding is described for the sub-set of study participants who were \<1 year of age at the time of randomization
|
2 Participants
n=12 Participants • Type of feeding is described for the sub-set of study participants who were \<1 year of age at the time of randomization
|
5 Participants
n=24 Participants • Type of feeding is described for the sub-set of study participants who were \<1 year of age at the time of randomization
|
PRIMARY outcome
Timeframe: 1 day (On admission to the pediatric intensive care unit (PICU) following CHD surgery)Blood 25OHD will be measured to determine vitamin D deficiency, with a concentration below 50 nmol/L used to define deficiency. A PICU admission blood sample could not be obtained for one patient in the Usual Care Group and one patient in the High Dose Group, thus the total number analyzed differs from the full sample size.
Outcome measures
| Measure |
Usual Care Group
n=19 Participants
This group will receive daily cholecalciferol (vitamin D3) based on the Adequate Intake (AI) for infants and the Recommended Dietary Allowance (RDA) for children over 1 year. Specific dose amounts are 400 IU per day for infants (0-1 year), and 600 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a placebo solution.
|
High Dose Group
n=20 Participants
This group will receive cholecalciferol (vitamin D3) based on the age-specific tolerable daily upper intake level (UL). Specific dose amounts are 1600 IU per day for infants (0-1 year), and 2400 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a dose of 1200 IU per day to account for vitamin D in formula.
Cholecalciferol: The High Dose group is based on the age-specific UL. These doses were chosen to elevate 25OHD well above 50 nmol/L, while minimizing the risk of vitamin D toxicity (e.g. hypercalcemia, hypercalciuria)
|
|---|---|---|
|
Blood 25 Hydroxyvitamin D (25OHD) Concentrations
|
34.8 nmol/L
Standard Deviation 12.0
|
52.0 nmol/L
Standard Deviation 23.3
|
SECONDARY outcome
Timeframe: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10Hypercalcemia will be defined as an ionized calcium level above 1.40 mmol/L; or above 1.45 mmol/L for children under 8 weeks. Hypercalcemia will be evaluated in blood collected immediately before CHD surgery and throughout the post-operative course (measurements are standard of care).
Outcome measures
| Measure |
Usual Care Group
n=20 Participants
This group will receive daily cholecalciferol (vitamin D3) based on the Adequate Intake (AI) for infants and the Recommended Dietary Allowance (RDA) for children over 1 year. Specific dose amounts are 400 IU per day for infants (0-1 year), and 600 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a placebo solution.
|
High Dose Group
n=21 Participants
This group will receive cholecalciferol (vitamin D3) based on the age-specific tolerable daily upper intake level (UL). Specific dose amounts are 1600 IU per day for infants (0-1 year), and 2400 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a dose of 1200 IU per day to account for vitamin D in formula.
Cholecalciferol: The High Dose group is based on the age-specific UL. These doses were chosen to elevate 25OHD well above 50 nmol/L, while minimizing the risk of vitamin D toxicity (e.g. hypercalcemia, hypercalciuria)
|
|---|---|---|
|
Number of Participants With Hypercalcemia as a Vitamin D Related Adverse Event
|
0 No. participants with hypercalcemia
|
0 No. participants with hypercalcemia
|
SECONDARY outcome
Timeframe: Immediately before surgery, on admission to the PICU following CHD surgery, and on the first post-operative dayHypercalciuria will be identified using calcium:creatinine ratios defined using age-specific norms and thresholds.
Outcome measures
| Measure |
Usual Care Group
n=20 Participants
This group will receive daily cholecalciferol (vitamin D3) based on the Adequate Intake (AI) for infants and the Recommended Dietary Allowance (RDA) for children over 1 year. Specific dose amounts are 400 IU per day for infants (0-1 year), and 600 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a placebo solution.
|
High Dose Group
n=21 Participants
This group will receive cholecalciferol (vitamin D3) based on the age-specific tolerable daily upper intake level (UL). Specific dose amounts are 1600 IU per day for infants (0-1 year), and 2400 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a dose of 1200 IU per day to account for vitamin D in formula.
Cholecalciferol: The High Dose group is based on the age-specific UL. These doses were chosen to elevate 25OHD well above 50 nmol/L, while minimizing the risk of vitamin D toxicity (e.g. hypercalcemia, hypercalciuria)
|
|---|---|---|
|
Number of Participants With Hypercalciuria
Enrolment
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hypercalciuria
Intra-operative
|
3 Participants
|
4 Participants
|
|
Number of Participants With Hypercalciuria
Post-Operative Day 1
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10Population: Data cannot be reported. Data was not collected.
Impaired vitamin D axis function will be defined as an inability to restore and maintain active hormone levels in the normal range following surgery after the first post-operative day
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10Population: This data cannot be reported. Data was not collected.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At any point between PICU admission and discharge, an average length of 5-7 days and not longer than 60 daysPopulation: Only the primary analysis (post-operative catecholamine requirements during the PICU admission will be evaluated as a dichotomous variable (yes/no)) was completed. Since there was not a significant difference between groups for this variable, we did not perform the secondary analysis (inotrope score).
Primarily, post-operative catecholamine requirements during the PICU admission will be evaluated as a dichotomous variable (yes/no). If a difference is noted in the primary analysis, inotrope requirements will be determined using the inotrope score, evaluated as the maximum score and in a time to event approach (off all inotropes, score of zero)
Outcome measures
| Measure |
Usual Care Group
n=20 Participants
This group will receive daily cholecalciferol (vitamin D3) based on the Adequate Intake (AI) for infants and the Recommended Dietary Allowance (RDA) for children over 1 year. Specific dose amounts are 400 IU per day for infants (0-1 year), and 600 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a placebo solution.
|
High Dose Group
n=21 Participants
This group will receive cholecalciferol (vitamin D3) based on the age-specific tolerable daily upper intake level (UL). Specific dose amounts are 1600 IU per day for infants (0-1 year), and 2400 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a dose of 1200 IU per day to account for vitamin D in formula.
Cholecalciferol: The High Dose group is based on the age-specific UL. These doses were chosen to elevate 25OHD well above 50 nmol/L, while minimizing the risk of vitamin D toxicity (e.g. hypercalcemia, hypercalciuria)
|
|---|---|---|
|
Post-operative PICU Catecholamine Requirements
|
15 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Post-operative day 1Population: This data cannot be reported. Data was not collected.
The post-operative day 1 echocardiogram will be used to evaluate for differences in cardiovascular function between study arms.
Outcome measures
Outcome data not reported
Adverse Events
Usual Care Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
High Dose Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Katie O'Hearn, PICU Research Coordinator
Children's Hospital of Eastern Ontario
Phone: 613-737-7600
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place