Vitamin D In the Prevention of Viral-induced Asthma in Preschoolers (DIVA)
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|ClinicalTrials.gov Identifier: NCT03365687|
Recruitment Status : Recruiting
First Posted : December 7, 2017
Last Update Posted : September 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|Asthma||Dietary Supplement: Vitamin D Dietary Supplement: Placebo||Phase 3|
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 infection 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).
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.
An intention-to-treat (ITT) analysis will be carried out with all randomised children.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||865 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This is a randomised, triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D3 supplementation.|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Masking Description:||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.|
|Official Title:||Vitamin D In the Prevention of Viral-induced Asthma in Preschoolers: a Randomized Controlled Multicenter Trial (DIVA)|
|Actual Study Start Date :||October 1, 2018|
|Estimated Primary Completion Date :||July 2023|
|Estimated Study Completion Date :||December 2023|
Active Comparator: Vitamin D
Vitamin D supplement (100,000 IU) orally at baseline and at 3.5 months with daily 400 IU vitamin D for 7 months
Dietary Supplement: Vitamin D
2 mL of 50,000 IU/mL at baseline and at 3.5 months with a daily dose of 1 mL (400 IU/mL) for 7 months
Other Name: Cholecalciferol
Placebo Comparator: Placebo
Placebo orally at baseline and at 3.5 months with daily placebo during 7 months
Dietary Supplement: Placebo
2 mL of placebo at baseline and at 3.5 months with a daily dose of placebo (1 mL) for 7 months
- Number of asthma exacerbations per child treated with rescue oral corticosteroids [ Time Frame: 7 months ]Group difference in the mean number of exacerbations treated with rescue oral corticosteroids/child
- Laboratory-confirmed respiratory infections [ Time Frame: 7 months ]Group difference in mean number of laboratory-confirmed respiratory infections during asthma exacerbations
- Severity of asthma symptoms during asthma exacerbations [ Time Frame: 7 months ]Group difference in the mean severity of asthma symptoms documented on the 'Asthma Flare-up Diary for Young Children'
- Duration of asthma symptoms during asthma exacerbations [ Time Frame: 7 months ]Group difference in the mean duration of asthma symptoms documented on the validated 'Asthma Flare-up Diary for Young Children'
- Intensity of use of rescue β2-agonists during asthma exacerbations [ Time Frame: 7 months ]Group difference in the mean cumulative use of rescue β2-agonists during exacerbations documented on the validated 'Asthma Flare-up Diary for Young Children'
- Parents' functional status during asthma exacerbations [ Time Frame: 7 months ]Group difference in the mean parents' functional status during exacerbation as documented on the validated 'Effect of a child's asthma flare-up on parents questionnaire'
- Mean number of ED visits for asthma exacerbations [ Time Frame: 7 months ]Group difference in mean number of ED visits for asthma exacerbations
- De-intensification of preventive asthma therapy [ Time Frame: 7 months ]Group difference in proportion of children with de-intensification of preventive asthma therapy
- Intervention cost-effectiveness [ Time Frame: 7 months ]Cost of intervention vs. cost (family expenses and health care) of exacerbations
- Hypercalciuria [ Time Frame: 7 months ]Group difference in the proportion of children with ≥1 occurrence of hypercalciuria (urinary calcium: creatinine ratio >1.38 mmol/mmol for children aged 1-<2 years, or >1.1 mmol/mmol for children aged 2-<5 years, or >0.77 mmol/mmol for children aged ≥5 years)
- Hypercalcemia [ Time Frame: 7 months ]Group difference in the proportion of children with clinically significant hypercalcemia (>2.63 mmol/L)
- Elevated serum 25-hydroxyvitamin D [ Time Frame: 7 months ]Group difference in the proportion of children with ≥1 occurrence of elevated serum 25OHD (greater than 250 nmol/L)
- Adverse Health Events [ Time Frame: 7 months ]Group difference in the distribution of adverse health events
- Gene expression [ Time Frame: 3.5 months ]Group difference in the change in gene expression levels (between baseline and 3.5 months) in blood peripherical mononuclear cells, adjusted for cell distribution estimated from lymphocyte differentiation in a subset of patients
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03365687
|Contact: Francine M Ducharme, MD||514-345-4931 ext email@example.com|
|Contact: Amina Hasanova, MSc||514-345-4931 ext firstname.lastname@example.org|
|Canada, British Columbia|
|British Columbia Children's Hospital||Recruiting|
|Vancouver, British Columbia, Canada, V6H 3V4|
|Contact: Connie Yang, MD 1-6048752000 ext 4931 email@example.com|
|Principal Investigator: Connie Yang, MD|
|Children's Hospital of London Health Sciences Centre||Recruiting|
|London, Ontario, Canada, N6A 2V5|
|Contact: Dirk Bock, MD 1-5196858824 Dirk.Bock@lhsc.on.ca|
|Principal Investigator: Dirk Bock, MD|
|Children's Hospital of Eastern Ontario||Recruiting|
|Ottawa, Ontario, Canada, K1H 8L1|
|Contact: Dhenuka Radhakrishnan, MD 1-6137377600 ext 2868 firstname.lastname@example.org|
|Principal Investigator: Dhenuka Radhakrishnan, MD|
|Montreal Children's Hospital||Recruiting|
|Montreal, Quebec, Canada, H3H 1P3|
|Contact: Reza Alizadehfar, MD email@example.com|
|Contact: Duncan Lejtenyi, MSc 1-514-412-4400 ext 22369 firstname.lastname@example.org|
|Principal Investigator: Reza Alizadehfar, MD|
|CHU Sainte Justine||Recruiting|
|Montreal, Quebec, Canada, H3T1C5|
|Contact: Sze Man Tse 514-345-4931 ext 54 email@example.com|
|Principal Investigator: Sze Man Tse|
|Montreal, Quebec, Canada|
|Contact: Marc-Andre Turcot, MD firstname.lastname@example.org|
|Principal Investigator: Marc-Andre Turcot|
|CHU de Québec-Université Laval||Recruiting|
|Québec, Quebec, Canada, G1V 4G2|
|Contact: Patrick Daigneault, MD Patrick.Daigneault@mail.chuq.qc.ca|
|Contact: Louise Gosselin 418-525-4444 ext 48290 email@example.com|
|Principal Investigator: Patrick Daigneault, MD|
|CHU de Sherbrooke||Active, not recruiting|
|Sherbrooke, Quebec, Canada, J1G 2E8|
|Principal Investigator:||Francine M Ducharme, MD||Study Principal Investigator|