Rapid Normalization of Vitamin D in Critically Ill Children: A Phase II Dose Evaluation Randomized Controlled Trial

NCT02452762 | Completed Phase 2 Results DMC

• 1 other identifier: VITdAL-PICU-01
• Study Type: interventional
• Target: 67
• Locations: 3 countries
• Sites: 4

Brief Summary

Documented roles for vitamin D in calcium homeostasis, cardiovascular and respiratory health, inflammation, innate immunity, and neuromuscular function have led to the hypothesis that deficiency might represent a modifiable risk factor for outcomes in critical illness. In recent years, dozens of adult studies have reported both high deficiency rates, and associations between lower vitamin D levels and organ dysfunction, health resource utilization, and mortality in the intensive care unit (ICU). More recently, similar observations have been made in critically ill pediatric populations. The cumulative body of basic science and clinical literature demonstrates that deficiency is common in critical illness and rapid normalization of vitamin D status could improve clinical outcomes and/or reduce health care costs. However, before conducting a phase III trial to determine whether restoration of vitamin D status improves outcomes in the PICU, the appropriate dosing regimen must be identified. Consequently, the investigators propose a phase II, double blind randomized controlled trial to determine a loading therapy dosing regimen that can safely and rapidly normalize vitamin D status in critically ill children.

Conditions

Hypovitaminosis D

Outcome Measures

Primary Outcomes (1)

• Vitamin D Status

  The percentage of critically ill children who achieve a blood 25OHD concentration above 75 nmol/L by day 7

  7 days

Secondary Outcomes (5)

• Patient Accrual Rate

  2 years

• Vitamin D Related Adverse Events

  On days 1, 2, 3, 7, hospital discharge (expected average of 2 weeks)

• Vitamin D Axis Function - Calcium

  On day 0, 3, 7, hospital discharge (expected average of 2 weeks)

• Vitamin D Axis Function - 1,25-dihydroxyvitamin D

  On day 3, 7, hospital discharge (expected average of 2 weeks)

• Immune Function - Cathelicidin

  On day 3, 7, hospital discharge (expected average of 2 weeks)

Study Arms (2)

Enteral Loading Arm

EXPERIMENTAL

Vitamin D3 (cholecalciferol) - Single dose at enrolment of 10000 IU/kg of cholecalciferol (max 400000 IU)

Drug: Vitamin D3

Placebo Arm

PLACEBO COMPARATOR

Patients will receive a placebo solution equivalent in volume to the dose of cholecalciferol administered to patients in the enteral loading arm.

Drug: Placebo

Interventions

Vitamin D3 DRUG

Also known as: Cholecalciferol

Enteral Loading Arm

Placebo DRUG

Placebo Arm

Eligibility Criteria

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

You may qualify if:

• (i) Admitted to ICU; (ii) Corrected gestational age \> 37 weeks to age \< 18 years; (iii) Expected ICU admission in excess of 48 hours and expected access for blood work at Day 7 of hospital admission; (iv) Blood 25OHD less than 50 nmol/L (regardless of prior approach to supplementation)

You may not qualify if:

• (i) Significant gastrointestinal disorder preventing enteral drug administration (e.g. necrotizing enterocolitis); (ii) Hypercalcemia (excluding transient abnormalities and those related to parenteral calcium administration for hypocalcemia); (iii) Confirmed or suspected William's syndrome; (iv) Patient known to have nephrolithiasis or Nephrocalcinosis; (v) Imminent plan for withdrawal of care or transfer to another ICU; (vi) Physician refusal; (vii) Previous enrollment in the study; (viii) Patient known to have granulomatous disease (tuberculosis or sarcoidosis), (ix) Severe liver dysfunction/liver failure; (x) Patient know to have hypersensitivity or allergy to vitamin D or any of the non-medicinal ingredients of the formulation; (xi) Patient on thiazide diuretics who is also receiving regular ongoing calcium supplementation above the daily recommended intake (for reasons other than hypocalcemia); (xii) Adolescent female of child-bearing age with a positive serum pregnancy test; or (xiii) Patient on digoxin-therapy

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead

Study Sites (4)

Medical University of Graz

Graz, 8036, Austria

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

Hospital Guillermo Grant Benavente

Concepción, Chile

Location

Related Publications (2)

• O'Hearn K, Menon K, Weiler HA, Amrein K, Fergusson D, Gunz A, Bustos R, Campos R, Catalan V, Roedl S, Tsampalieros A, Barrowman N, Geier P, Henderson M, Khamessan A, Lawson ML, McIntyre L, Redpath S, Jones G, Kaufmann M, McNally D; Canadian Critical Care Trials Group. A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study). BMC Pediatr. 2023 Aug 14;23(1):397. doi: 10.1186/s12887-023-04205-9.

  PMID: 37580663 DERIVED

• McNally D, Amrein K, O'Hearn K, Fergusson D, Geier P, Henderson M, Khamessan A, Lawson ML, McIntyre L, Redpath S, Weiler HA, Menon K; Canadian Critical Care Trials Group. Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study). Pilot Feasibility Stud. 2017 Dec 8;3:70. doi: 10.1186/s40814-017-0214-z. eCollection 2017.

  PMID: 29234503 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

Results Point of Contact

• Title: James Dayre McNally, Principal Investigator and Pediatric Intensivist
• Organization: Children's Hospital of Eastern Ontario

dmcnally@cheo.on.ca

613-737-7600

Study Officials

• James D McNally

  Children's Hospital of Eastern Ontario

  PRINCIPAL INVESTIGATOR

• Menon Kusum

  Children's Hospital of Eastern Ontario

  STUDY CHAIR

• McIntyre Lauralyn

  The Ottawa Hospital

  STUDY CHAIR

• Fergusson Dean

  The Ottawa Hospital

  STUDY CHAIR

• Amrein Karin

  Medical University of Graz

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Intensivist

Study Record Dates

• First Submitted: May 15, 2015
• First Posted: May 25, 2015
• Study Start: January 1, 2016
• Primary Completion: November 1, 2017
• Study Completion: January 1, 2018
• Last Updated: August 13, 2021
• Results First Posted: August 13, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CL (1); CA (2)