Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): protocol for a multicentre randomised placebo-controlled triple-blind trial

Megan E Jensen, Francine M Ducharme, Nathalie Alos, Geneviève Mailhot, Benoît Mâsse, John H White, Mohsen Sadatsafavi, Ali Khamessan, Sze Man Tse, Reza Alizadehfar, Dirk E Bock, Patrick Daigneault, Chantal Lemire, Connie Yang, Dhenuka Radhakrishnan, Megan E Jensen, Francine M Ducharme, Nathalie Alos, Geneviève Mailhot, Benoît Mâsse, John H White, Mohsen Sadatsafavi, Ali Khamessan, Sze Man Tse, Reza Alizadehfar, Dirk E Bock, Patrick Daigneault, Chantal Lemire, Connie Yang, Dhenuka Radhakrishnan

Abstract

Introduction: Preschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the fall or winter. Vitamin D insufficiency is highly prevalent in Canadian preschoolers with recurrent asthma exacerbations, particularly in winter. It is associated with more URTIs and, in patients with asthma, more oral corticosteroid (OCS) use. Although evidence suggests that vitamin D supplements significantly decrease URTIs and asthma exacerbations requiring OCS, there is insufficient data in preschoolers. This study aims to determine the impact of vitamin D3 supplementation on exacerbations requiring OCS, in preschoolers with recurrent URTI-induced asthma exacerbations.

Methods and analysis: This is a phase III, randomised, triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D3 supplementation in children aged 1-5 years, with asthma triggered by URTIs and a recent history of frequent URTIs and OCS use. Children (n=865) will be recruited in the fall and early winter and followed for 7 months. They will be randomised to either the (1) intervention: two oral boluses of 100 000 international unit (IU) vitamin D3 (3.5 months apart) with 400 IU vitamin D3 daily; or (2) control: identical placebo boluses with daily placebo. The primary outcome is the number of exacerbations requiring OCS per child, documented by medical and pharmacy records. Secondary outcomes include number of laboratory-confirmed viral URTIs, exacerbation duration and severity, parent functional status, healthcare use, treatment deintensification, cost and safety.

Ethics and dissemination: This study has received ethical approval from all sites. Results will be disseminated via international conferences and manuscripts targeting paediatricians and respirologists, and to families of asthmatic children via our Quebec parents-partners outreach programme. If proven effective, findings may markedly influence the management of URTI-induced asthma in high-morbidity preschoolers and could be directly implemented into practice with an update to clinical guidelines.

Trial registration number: NCT03365687.

Keywords: asthma; nutrition & dietetics; paediatric thoracic medicine; statistics & research methods.

Conflict of interest statement

Competing interests: By partnership agreement, Euro-Pharm International Canada Inc. (Montreal, QC Canada), and their representative (Ali Khamessan) donated all vitamin D study preparations. Dr Khamessan is responsible for the formulation of the placebo and high dose vitamin D preparation; however, neither Dr Khamessan, nor Euro-Pharm International Canada Inc., had any input into other aspects of study design, and will have no involvement in analysis or interpretation of results.The authors have no competing interests.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study design and participant flow through the 7±0.5 month study.

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