Rapid Normalization of Vitamin D Deficiency in PICU

NCT03742505 | Completed Phase 3 DMC

• 1 other identifier: VITdALIZE-KIDS
• Study Type: interventional
• Target: 424
• Locations: 1 country
• Sites: 10

Brief Summary

Vitamin D plays an important role in calcium balance, heart and lung health, inflammation, infection prevention, and muscle strength. Due to these roles, it has been suggested that critically ill patients with low vitamin D levels might have higher rates of death and worse long-term health. We believe that identifying critically ill children with vitamin D deficiency and then restoring vitamin D levels quickly could represent a safe, easy and inexpensive means of reducing patient illness, preventing death and improving quality of life. This clinical trial will determine whether rapid normalization of vitamin D deficiency improves survival and health-related quality of life following critical illness. The VITdALIZE-KIDS trial is a multicentre randomized clinical trial in Canadian Pediatric Intensive Care Units (PICUs). Critically ill children who agree to participate (consent given by caregivers) will have their blood vitamin D level measured, and those who are vitamin D deficient will be randomized to receive a single dose of either high-dose vitamin D3 or placebo (no drug). Study participants assigned to the high-dose vitamin D arm will receive 10,000 IU/kg of enteral cholecalciferol (up to a maximum of 400,000 IU). We have tested this dose in a pilot trial, and no patient experienced serious adverse events related to vitamin D administration. Patients will be followed for 90 days to determine whether they survived and had a significant change in their health and quality of life. Vitamin D deficiency is a common problem not only among critically ill Canadian children, but in PICUs worldwide. In addition to being applicable in Canada, our study protocol was designed to be generalizable and meaningful to critically ill children worldwide.

Conditions

Vitamin D Deficiency

Outcome Measures

Primary Outcomes (1)

• Health related quality of life

  The primary outcome will be health related quality of life. Health related quality of life will be measures using the age-appropriate PedsQL scale (Ages: 2-7, PedsQL 4.0 Generic Core Scales; Ages 1-24 months: PedsQL™ Infant Core Scales (1-24 months). The PedsQL requires only 23 items to score (36 items for the infant scales), a task easily completed in 5-7 minutes and assesses four domains: physical, emotional, social, and school functioning. The mean PedsQL Core Scale is equal to the sum of all items over the number of items answered on all the Scales and generates a number out of 100. The scoring for the scale is the same for both the PedsQL 4.0 Generic Core Scale and PedsQL Infant Core Scale, allowing the score from either scale to be reported together as one outcome.

  28 days

Secondary Outcomes (1)

• New and/or progressive multiple organ dysfunction

  28 days

Other Outcomes (14)

• Functional status

  28 and 90 days

• Mortality

  28 and 90 days

• PICU length of stay

  Up to 90 days post-randomization

Study Arms (2)

Vitamin D

EXPERIMENTAL

Approximately half of the subjects randomized into VITdALIZE-KIDS will be randomized into the Vitamin D Group and will receive a single dose of cholecalciferol at enrolment. Participants may also receive standard vitamin D dosing at the discretion of the care team (e.g. 400-1000 IU/day).

Drug: Cholecalciferol

Placebo

PLACEBO COMPARATOR

Approximately half of the subjects randomized into VITdALIZE-KIDS will be randomized into the Placebo Group and will receive a single dose of placebo at enrolment. Participants may also receive standard vitamin D dosing at the discretion of the care team (e.g. 400-1000 IU/day).

Other: Placebo

Interventions

Cholecalciferol DRUG

Single enteral cholecalciferol load at a dose of 10,000 IU/kg (maximum 400,000 IU)

Vitamin D

Placebo OTHER

Single enteral placebo dose equivalent in volume to the appropriate weight-based dose of cholecalciferol

Placebo

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Admitted to PICU
• Corrected gestational age 37 weeks to age 18 years
• Vitamin D deficiency, as defined by blood 25OHD \< 50 nmol/L at the time of screening

You may not qualify if:

• Patient will be discharged from PICU before they can be enrolled (i.e. study drug administered) into the VITdALIZE-KIDS study and/or patient will be in hospital for \<3 days following enrollment
• Treating physician refuses enteral drug administration due to gastrointestinal disorder, and expects to do so for the full duration of the patient's PICU admission
• Persistent hypercalcemia (ionized calcium \>1.40 mmol/L (age \>2 months), \>1.45 (age \<2 months) excluding transient abnormalities and those related to parenteral calcium administration for hypocalcemia;
• Confirmed or suspected William's syndrome;
• Known nephrolithiasis or nephrocalcinosis;
• Imminent plan for withdrawal of treatment or transfer to another ICU not participating in the VITdALIZE-KIDS trial;
• Physician refusal;
• Previous enrollment in this trial;
• Granulomatous disease (tuberculosis or sarcoidosis);
• Severe liver failure;
• Hypersensitivity or allergy to vitamin D or any of the non-medicinal ingredients of the formulation;
• Patient on thiazide diuretics also receiving regular ongoing calcium supplementation above the daily recommended intake;
• Adolescent female of child-bearing age with a positive pregnancy serum test;
• Patient on digoxin-therapy; and
• Treating physician intends to administer vitamin D doses above 1000 IU (e.g. patient presents with isolated clinical symptoms of severe VDD, severe burns).

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• EURO-PHARM International Canada, Inc.: collaborator
• Canadian Critical Care Trials Group: collaborator

Study Sites (10)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T5J 3E4, Canada

Location

BC Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Division of Critical Care, Department of Pediatrics, Victoria Hospital

London, Ontario, N6C 3T6, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Centre hospitalier universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (1)

• O'Hearn K, Menon K, Albrecht L, Amrein K, Britz-McKibbin P, Cayouette F, Choong K, Foster JR, Fergusson DA, Floh A, Fontela P, Geier P, Gilfoyle E, Guerra GG, Gunz A, Helmeczi E, Khamessan A, Joffe AR, Lee L, McIntyre L, Murthy S, Parsons SJ, Ramsay T, Ryerson L, Tucci M, McNally D; Canadian Critical Care Trials Group. Rapid normalization of vitamin D deficiency in PICU (VITdALIZE-KIDS): study protocol for a phase III, multicenter randomized controlled trial. Trials. 2024 Sep 19;25(1):619. doi: 10.1186/s13063-024-08461-7.

  PMID: 39300483 DERIVED

MeSH Terms

Conditions

Vitamin D Deficiency

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Dayre McNally, MD, PhD

  Children's Hospital of Eastern Ontario

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The randomization lists will only be accessible to the Methods Centre at the Ottawa Hospital Research Institute and the research pharmacist(s). The active drug and placebo are identical (e.g. colour, consistency, volume, taste, smell, containers).
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Intensivist

Model Details: Pragmatic, Phase III, multi-centre, double-blinded randomized controlled trial

Study Record Dates

• First Submitted: November 12, 2018
• First Posted: November 15, 2018
• Study Start: June 17, 2019
• Primary Completion: October 17, 2024
• Study Completion: October 17, 2024
• Last Updated: February 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (10)