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 (HICCUPS 2)
Our research group has shown that almost all children with congenital heart disease (CHD) are vitamin D deficient following heart surgery. This work strongly suggests that the vitamin D intake presently recommended for healthy children, and also given to children with CHD, is inadequate to prevent vitamin D deficiency following surgery. Unfortunately, there have been no studies investigating any other vitamin D dose in children with heart disease. Recently, a higher dose of vitamin D intake has been approved (by the Institute of Medicine and Health Canada) and recent work on healthy children has shown it to be safe. The objective of this study is to determine whether this recently approved higher dose of vitamin D can safely reduce the number of children who are vitamin D deficient following surgery. This dose evaluation study will also evaluate whether it is possible to perform a large study (across Canada) to determine whether vitamin D supplementation can improve outcomes following surgery. It is hypothesized that a daily high dose vitamin D regimen, modeled on the Institute of Medicine daily upper tolerable intake level (UL), will significantly reduce vitamin D deficiency following CHD surgery, when compared with usual intake.
Vitamin D Deficiency
Heart Defects, Congenital
Dietary Supplement: Cholecalciferol
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Prevention of Post-Cardiac Surgery Vitamin D Deficiency in Children With Congenital Heart Disease: A Pilot Dose Evaluation Randomized Controlled Trial|
- Blood 25 hydroxyvitamin D (25OHD) concentrations [ Time Frame: 1 day (On admission to the pediatric intensive care unit (PICU) following CHD surgery) ] [ Designated as safety issue: No ]Blood 25OHD will be measured to determine vitamin D deficiency, with a concentration below 50 nmol/L used to define deficiency.
- Hypercalcemia as a Vitamin D related adverse event [ Time Frame: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10 ] [ Designated as safety issue: Yes ]Hypercalcemia 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).
- Hypercalcuria as a vitamin D related adverse event [ Time Frame: Immediately before surgery, on admission to the PICU following CHD surgery, and on the first post-operative day ] [ Designated as safety issue: Yes ]Hypercalcuria will be identified using calcium:creatine ratios defined using age-specific norms and thresholds
- Vitamin D parathyroid renal axis function through changes in blood 1,25-dihydroxycholecalciferol [ Time Frame: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10 ] [ Designated as safety issue: No ]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
- Changes in cathelicidin as measure of innate immune function [ Time Frame: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10 ] [ Designated as safety issue: No ]
- Post-operative PICU catecholamine requirements [ Time Frame: At any point between PICU admission and discharge, an average length of 5-7 days and not longer than 60 days ] [ Designated as safety issue: No ]Primarily, post-operative catecholamine requirements during the PICU admission will be evaluated as a dichotomous variable (yes/no). Secondarily, inotrope requirements will be determine using the inotrope score, evaluated as the maximum score and in a time to event approach (off all inotropes, score of zero)
- Cardiovascular function through an echocardiogram [ Time Frame: Post-operative day 1 ] [ Designated as safety issue: No ]The post-operative day 1 echocardiogram will be used to evaluate for differences in cardiovascular function between study arms.
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
No Intervention: 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.
Experimental: 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.
Dietary Supplement: 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)
Other Name: Vitamin D3
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01838447
|Contact: James D McNally, M.D., Ph.D.||613-737-7600 ext firstname.lastname@example.org|
|Children's Hospital of Eastern Ontario||Recruiting|
|Ottawa, Ontario, Canada, K1H 8L1|
|Contact: Tara Girolamo, RN, B.Sc.N. 613-737-7600 ext 3639 email@example.com|
|Contact: Katharine J O'Hearn, M.Sc. 613-737-7600 ext 4006 firstname.lastname@example.org|
|Principal Investigator: James D McNally, M.D., Ph.D.|
|Sub-Investigator: Kusum Menon, M.D.|
|Sub-Investigator: Gyaandeo Maharajh, M.D., C.M.|
|Sub-Investigator: Margaret Lawson, M.D.|
|Sub-Investigator: Osama Y Al-Dirbashi, Ph.D.|
|Sub-Investigator: Stephanie Redpath, MD|
|Sub-Investigator: Jane Loughead, MD|
|Principal Investigator:||James D McNally, M.D., Ph.D.||Children's Hospital of Eastern Ontario|
|Study Chair:||Kusum Menon, M.D.||Children's Hospital of Eastern Ontario|
|Study Chair:||Lauralyn McIntyre, M.D.||Ottawa Hospital|
|Study Chair:||Dermot R Doherty, M.B., B.Ch.||Temple Street Children's University Hospital Dublin and University College|
|Study Chair:||Dean Ferguson, Ph.D.||Ottawa Hospital Research Institute|
|Study Chair:||Hope Weiler, Ph.D.||McGill University|