vitamin d in preschoolers with viral-induced asthma

Conditions: Asthma

Summary: in this 7-month randomized controlled trial, children aged 1-6 years with asthma attacks triggered mostly by colds, will receive a high dose of vitamin d or a placebo every 3.5 months during their usual clinic visit. this study will test whether children receiving a high dose of vitamin d have less frequent and less severe asthma exacerbations compared with those receiving placebo.the study will also document the safety profile of this strategy.

important note: due to receiving a 2-year partial funding enabling only a single-centre pilot trial, rather than an adequately-powered multicentre study, the primary outcome was modified post hoc for the overall change from baseline in total serum 25ohd during the study as well as at 3.5 and 7 months, similar to our previous pilot study.(nct01999907) post hoc secondary outcomes included the group difference in the proportion of children with total 25ohd ≥75 nmol/l at 3.5 and 7 months and in the rate of oral corticosteroid courses per child. other a priory specified outcomes included the proportion of children with hypercalciuria (ca:cr) \>1.25 (1-2 years), \>1 (2-5 years) nmol/nmol at any point in time; proportion of children with ≥1 exacerbation requiring rescue oral steroids (former primary outcome); number of emergency department (ed) visits; intensity and duration of asthma symptoms and cumulative use of rescue ß2-agonist use, documented on asthma flare-up diary for young children (adyc); the impact of parents' functional status during exacerbations ascertained on the effect of a child's asthma flare-up on parents; and duration of urti. based on this analysis of this new post-hoc primary outcome, we have changed the intervention and the primary outcome and obtained funding for a new large multicentre study nct03365687. it is thus important to share the results of this current trial with other investigators prior reported description design: a multicenter triple-blind randomized parallel-group, placebo-controlled trial of vitamin d3 supplementation. children aged 1-5 years with (i) physician-diagnosed asthma, predominantly triggered by upper respiratory tract infections (urtis), (ii) ≥4 reported urtis in the past year, and (iii) ≥1 exacerbation requiring ocs (a recognised marker of moderate and severe exacerbations) in the past 6 months or ≥2 in the past 12 months, will be randomly allocated to one of two treatments in blocks of 4-6, stratified on recruitment site: intervention group (n=432)-100,000 iu oral vitamin d3; control group (n=432)-identical placebo, for 2 oral doses, 3.5 months apart. co-intervention with asthma therapy (preventive or pre-emptive ics) will be left to the discretion of the physician and documented. children will be followed every 3.5 months as per usual practice, with a home visit 10 days after each bolus, during which urine and blood will be sampled for urinary calcium:creatinine ratio, serum vitamin d, markers of calcium metabolism, and mechanistic exploration. a validated diary will serve to document the intensity and severity of exacerbations. in two sites, preschool lung function will be documented (if ≥ 3yrs). outcomes: primary endpoint-number of exacerbations requiring rescue oral corticosteroids (ocs) per child, documented by medical and pharmacy records. secondary outcomes: duration and severity of exacerbations (symptoms \& β2-agonist use, by diary; emergency visits, by medical records), parental functional status (by validated instrument), asthma therapy intensification and health care and direct costs (by health records \& parent reports). safety, mechanistic, exploratory outcomes: hypercalciuria, calcium metabolism, excess vitamin d, change in serum gene expression at 10 days (first 25 patients); and change from baseline at 7 months in preschool lung function (2 sites). based on 3 published rcts, a sample of 432 per arm (400+7.5% attrition) will provide 80% power (2-tailed alpha of 5%) to detect a 25% reduction in number of exacerbations requiring ocs/child (0.55 vs. 0.4125).

Eligibility criteria:
inclusion criteria: * age 1-5 years * physician-diagnosed asthma as per the global initiative for asthma (gina) guidelines * urtis as the main asthma trigger (parental report) * ≥4 urtis in the past 12 months (parental report) * ≥1 asthma exacerbation requiring rescue oral corticosteroids (ocs) in the past 6 months or ≥2 in the past 12 months exclusion criteria: * intake or intention to use more than 400 iu/day of vitamin d supplement * extreme prematurity (\<28 weeks gestation) * infants \<12 months of age * no vitamin d supplementation when breast-fed * recent (\<1 year) immigrants from a region at high risk of rickets * children with vitamin d restrictive diets e.g. vegans * other chronic respiratory disease (broncho-pulmonary dysplasia; cystic fibrosis) * condition(s) that alter calcium or vitamin d metabolism/absorption (hypo/hyperparathyroidism, kidney/liver disease, inflammatory bowel disease) * medications that interfere with vitamin d metabolism (anti-epileptics, diuretics, antacids, anti-fungal drug) * vitamin d supplementation \>1000 iu/ day in last 3 months * anticipated difficult follow-up (unable to attend clinic visits; plan to leave the province).

Keywords: rct asthma pediatric virus corticosteroid