Vitamin D In the Prevention of Viral-induced Asthma in Preschoolers: a Randomized Controlled Multicenter Trial (DIVA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 323
- 试验地点
- 17
- 主要终点
- Number of asthma exacerbations per child treated with rescue oral corticosteroids
研究概览
简要总结
In this 7-month randomized controlled trial, children aged 1 to less than 6 years, with recurrent 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, and a daily supplement of vitamin D or a placebo. This study will test whether children in vitamin D group have less frequent and less severe asthma exacerbations compared with those receiving placebo.The study will also document the safety profile of this strategy.
详细描述
This is a multicenter triple-blind randomized parallel-group, placebo-controlled trial of vitamin D3 supplementation. Children aged 1-5 (<6) years with physician-diagnosed asthma predominantly triggered by upper respiratory tract infections will be screened for enrolment in paediatric asthma, respiratory or allergy clinics and the ED departments and randomized between Sept 1 to January 31, annually (4 recruitment years) and year around from 2022 onwards.
Using a computer-generated random list, stratified by site, children will be allocated (1:1) using permuted block randomisation method to enhance concealment.
Children will be followed for 7 months, with 3 visits every 3.5 months with repeated urine (for calcium:creatinine ratio) and blood samples. In addition, ten (10) days after each bolus, urine will be sampled for urinary calcium:creatinine ratio. In case of elevated urine calcium:creatinine ratio, a blood sample may be needed primarily for markers of calcium metabolism and exploratory outcomes. Only patients enrolled at CHU Sainte-Justine and Montreal Children's Hospital will receive a systematic home visit 10 days after first bolus for both urine and blood samples. There will be 6 follow-up phone calls, at week 1 and then monthly, to inquire about exacerbations and URTIs, remind parents to complete questionnaires and to collect a nasal swab at each exacerbation and screen for adverse events.
The main outcome is the number of courses of rescue oral corticosteroids (OCS) per child during the study period. Several secondary outcomes will be documented using biological samples and validated questionnaires to ascertain laboratory-confirmed respiratory infections, intensity and severity of exacerbations, mean number of ED visits, parents' functional status during exacerbations, de-intensification of preventive asthma therapy, cost effectiveness, and safety profile.
A sample of 432 children (400+7,5% attrition) per arm will provide 80% power with a two-tailed alpha of 5% to detect a 25% relative reduction in the mean number of exacerbations requiring OCS per child.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The manufacturer, Europharm, will provide the active vitamin D3 and placebo preparations, identical in appearance and taste, in coded latex-free bottles. A web-based randomisation system will allow Site pharmacies to obtain allocated treatment number, prepare the 2 mL bolus in coded syringes and the coded bottles containing the daily dose, and dispense study drugs in masked kits.
入排标准
- 年龄范围
- 1 Year 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 1-5 years
- •Physician-diagnosed asthma (as per the 2015 Canadian Position Paper on the diagnosis of preschool asthma)
- •≥1 asthma exacerbation requiring rescue oral corticosteroids (OCS) in the past 6 months or ≥2 in the past 12 months; or from the pandemic (2020) onwards, ≥1 asthma exacerbation requiring rescue oral corticosteroids (OCS) in the past 12 months (as documented by pharmacy/medical records)
- •≥4 upper respiratory tract infections (URTIs) in the past 12 months (as per parental report); or from the pandemic (2020) onwards, ≥ 2 URTIs in past 12 months
- •URTIs as the main asthma trigger (as per parental report)
排除标准
- •Intake > 400 IU/day of vitamin D3 supplements or fish oil in the past 3 months
- •Intention to use > 400 IU/day of vitamin D3 supplements or fish oil in the fall and winter
- •Extreme prematurity (< 28 week gestation)
- •No vitamin D supplementation (if breast-fed in the last 6 months)
- •Vitamin D restrictive diets, that is, minimal intake of vitamin D fortified milk (<250 mL/day for 1-3 years or <375 mL/day for 4-6 years AND no other (or <200 IU/day) vitamin D supplement
- •Recent immigrants from regions at high risk of rickets (in the past 12 months)
- •Recent refugees (in the past 12 months)
- •Undernourished children
- •Other chronic respiratory disease (e.g. Cystic fibrosis, Bronchopulmonary dysplasia) or chronic kidney, gastrointestinal, endocrinological or cardiac diseases, or sickle cell anemia
- •History of bone disorder disease (e.g. rickets, osteomalacia)
- •Intake of oral anti-epileptic, diuretic or anti-fungal medications
- •Anticipated difficulty with follow-up or with adherence to the intervention or the procedures
结局指标
主要结局
Number of asthma exacerbations per child treated with rescue oral corticosteroids
时间窗: 7 months
Group difference in the mean number of exacerbations treated with rescue oral corticosteroids/child
次要结局
- Laboratory-confirmed respiratory infections(7 months)
- Mean number of ED visits and hospital admissions for asthma exacerbations(7 months)
- De-intensification of preventive asthma therapy(3.5 and 7 months)
- Duration of asthma symptoms during asthma exacerbations(7 months)
- Duration of B2-agonist use during asthma exacerbations(7 months)
- Severity of asthma symptoms during asthma exacerbations(7 months)
- Intensity of use of rescue β2-agonists during asthma exacerbations(7 months)
- Parents' functional status during asthma exacerbations(7 months)
- Number of parental workdays lost(7 months)
- Parental productivity(7 months)
- Intervention cost-effectiveness(7 months)
研究者
Professor Francine Ducharme
Pediatrician
St. Justine's Hospital