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Trial registered on ANZCTR


Registration number
ACTRN12616000659404
Ethics application status
Approved
Date submitted
25/01/2016
Date registered
20/05/2016
Date last updated
23/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
PREVARID - PREVention of Acute Respiratory Infections with Vitamin D
Scientific title
Does vitamin D supplementation prevent acute respiratory infection health care visits among children under 2 years old? A randomised controlled trial
Secondary ID [1] 288339 0
Nil known
Universal Trial Number (UTN)
u1111-1178-6233
Trial acronym
PREVARID - PREVention of Acute Respiratory Infections with Vitamin D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
acute respiratory infection (ARI) 297316 0
Condition category
Condition code
Respiratory 298009 298009 0 0
Normal development and function of the respiratory system
Infection 298771 298771 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Determine if weekly vitamin D supplementation with vitamin D (5000 IU) for 12 months after Acute Lower Respiratory Infections (ALRI) hospital admission prevents subsequent health care ARI visits. The study medicine will be in a bottle with a dropper. Each participant will be given 5 drops orally administered of study medicine per week, with all 5 drops given on the same day each week. Adherence will be monitored by weighing the study medicine bottles and by parental interview.
Intervention code [1] 293640 0
Prevention
Comparator / control treatment
Placebo. The placebo composition is based in coconut oil.
Control group
Placebo

Outcomes
Primary outcome [1] 297074 0
Number of ARI presentations to health care. This primary outcomes will be determined from review of primary and secondary care health care records
Timepoint [1] 297074 0
12 months after the enrollment of the child in the RCT.
Primary outcome [2] 297602 0
Number of ARI presentations to hospital emergency departments.This primary outcomes will be determined from review of public hospital presentations contained in the National Minimum Dataset
Timepoint [2] 297602 0
12 months after the enrollment of the child in the RCT.
Primary outcome [3] 297603 0
Number of ARI hospital admissions. This primary outcomes will be determined from review of public hospital presentations contained in the National Minimum Dataset
Timepoint [3] 297603 0
12 months after the enrollment of the child in the RCT.
Secondary outcome [1] 319981 0
Number of antibiotic prescriptions dispensed during the 12 months following study enrolment. Antibiotics prescriptions dispensed from community pharmacies will be determined from the Pharmaceutical Collection, a national administrative dataset comprising records of subsidized prescription medications dispensed from community pharmacies. Antibiotics prescriptions dispensed from hospital pharmacies will be determined from a review of the hospital electronic health care record.
Timepoint [1] 319981 0
12 months after the enrollment of the child in the RCT.
Secondary outcome [2] 323941 0
Serum 25(OH)D concentration will be assessed at baseline and 6 months, plus at 12 months in a 10% subsample.
Timepoint [2] 323941 0
6 months after study enrolment and, in 10% of the enrolled subjects, 12 months after study enrolment.

Eligibility
Key inclusion criteria
Children will be eligible for enrolment if they are NZ residents, are <2 years old at the time of their ALRI hospital admission and reside in the Auckland District Health Board catchment area.
Minimum age
0 Days
Maximum age
2 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children will be ineligible if receiving vitamin D supplements or if they have a complex chronic condition known to be associated with recurrent hospital admission, for example, cystic fibrosis or a tracheostomy.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Study medicine bottles for the 2 groups (intervention and placebo) will be identical in colour, shape, and volume and the study medicine identical in colour, consistency, and taste. Allocation concealment will be achieved by using numbered containers.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation to the 2 study arms (intervention and placebo) will be by restricted randomization within blocks of variable size using a computer generated randomisation list.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
It will be a randomised double-blinded placebo-controlled parallel study.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data will be directly entered into an electronic database using REDCapTM (Research Electronic Data capture System). Analyses will be performed on the intended to treat population. All comparisons of the treatment and placebo arms will be performed using two-sided tests at a 0.05 significance level. The null hypothesis for all analyses is that there is no difference between the treatment arms. Proportions will be compared using the chi-square test and Fisher’s exact test, and interval level data using the Wilcoxon rank sum test. The number needed to treat (NNT) will be calculated as 1/(absolute risk reduction).

From the description within the Growing Up in New Zealand child cohort study of community pharmacy antibiotic prescribing data in children < 5 years old we know that the number of antibiotic prescriptions dispensed from age 0 to 18 months (n = 17478) and from age 19 to 36 months (n = 18055) is roughly equal.

As acute respiratory infections are the primary determinant of antibiotic prescribing in early childhood we assume that if there is a mean of 5.3 primary care ARI presentations from age 0 to 18 months then there will be a mean of approximately 10 primary care ARI visits from age 0 to 36 months. With the same standard deviation of 4.2 then to detect a 15% reduction in primary care visits (approximately difference found in the international individual patient data meta-analysis ARI study) we would need 236 children in our study (118 in treatment, 118 in placebo). We anticipate an attrition of 20% so we are enrolling a sample of 300 in order to have a sample of 236 that complete the study.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7529 0
New Zealand
State/province [1] 7529 0
Auckland

Funding & Sponsors
Funding source category [1] 292702 0
Other
Name [1] 292702 0
Cure Kids
Address [1] 292702 0
Laundry Building. Suite 4, level 4. 58 Surrey Cresent. Grey Lynn. Post Code:1021. Auckland.
Country [1] 292702 0
New Zealand
Primary sponsor type
Other
Name
Cure Kids
Address
Laundry Building. Suite 4, level 4. 58 Surrey Cresent. Grey Lynn. Post Code:1021. Auckland.
Country
New Zealand
Secondary sponsor category [1] 291432 0
None
Name [1] 291432 0
Address [1] 291432 0
Country [1] 291432 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294184 0
Health and Disability Ethics Committee
Ethics committee address [1] 294184 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011
Ethics committee country [1] 294184 0
New Zealand
Date submitted for ethics approval [1] 294184 0
23/03/2016
Approval date [1] 294184 0
19/05/2016
Ethics approval number [1] 294184 0
16/NTB/57
Ethics committee name [2] 294185 0
Standing Committee on Therapeutic Trials (SCOTT).
Ethics committee address [2] 294185 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011
Ethics committee country [2] 294185 0
New Zealand
Date submitted for ethics approval [2] 294185 0
31/05/2016
Approval date [2] 294185 0
Ethics approval number [2] 294185 0

Summary
Brief summary
During the first two years of life a child living in New Zealand (NZ) is more than twice as likely as a child living in England or the United States to require inpatient hospital care for an acute lower respiratory infection (ALRI). In NZ 10% of children <2 years old are hospitalised with an acute respiratory infection with 80% of these being acute lower respiratory infections (ALRI). Respiratory infections account for two-thirds of all infectious disease hospital admissions in this age group. Over 50% of newborns in NZ are vitamin D deficient. We showed that, in Auckland, the risk of vitamin D deficiency from age 6-23 months of age is 7 times greater for Pacific and 3 times greater for Maori compared with European children, and 4 times greater for children living in crowded households.
We have recently shown, in a randomised controlled trial (RCT) in Auckland, that vitamin D supplementation given during the last trimester of pregnancy and then from birth to age 6 months prevents acute respiratory infection (ARI) primary care visits from birth to age 18 months. Of the 260 pregnant women enrolled into this trial 49% were Pacific and 24% were Maori. For over a quarter of the children <2 years old who are hospitalised with an ALRI, this is just the first of a series of ALRIs that require inpatient hospital care.
In this project we will determine if vitamin D supplementation given to children <2 years old who are hospitalised with an ALRI reduce, in the next 12 months, the number of ARI health care visits they make. We will do this by conducting a hospital based RCT. We will enrol children <2 years old admitted to Starship Children’s Hospital with an ALRI with recruitment occurring over the autumn, winter and spring months (with extension in a second autumn/winter/spring time period if necessary, and randomly assign them to weekly vitamin D supplementation or placebo for 12 months after this ALRI hospital admission. We will follow these children over this 12 month period and describe their respiratory illnesses, nutrition, sunlight exposure and household living conditions. We will identify primary and secondary care ARI visits from primary care records and from the Ministry of Health national hospital event dataset (the National Minimum Dataset). Blood samples will be obtained for measurement of 25(OH)D concentration at enrolment and 6 months after randomisation. Measurement of 25(OH)D concentration at 12 months after enrolment will be done in a random subsample of 10% of the children enrolled in the study.
Should this trial show that vitamin D supplementation prevents subsequent health care ARI visits, then such supplementation will be included in the Starship Clinical guidelines as a component of routine and best practice clinical care. These guidelines are used by paediatricians working throughout NZ to inform their care of children admitted to hospital.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62646 0
A/Prof Cameron Grant
Address 62646 0
Department of Paediatrics: Child & Youth Health. University of Auckland. Private Bag 92019 Wellesley Street, Auckland. Post Code 1142
Country 62646 0
New Zealand
Phone 62646 0
+64099236192
Fax 62646 0
+64093737486
Email 62646 0
cc.grant@auckland.ac.nz
Contact person for public queries
Name 62647 0
A/Prof Cameron Grant
Address 62647 0
Department of Paediatrics: Child & Youth Health. University of Auckland. Private Bag 92019 Wellesley Street, Auckland Post Code 1142
Country 62647 0
New Zealand
Phone 62647 0
+64099236192
Fax 62647 0
+64093737486
Email 62647 0
cc.grant@auckland.ac.nz
Contact person for scientific queries
Name 62648 0
A/Prof Cameron Grant
Address 62648 0
Department of Paediatrics: Child & Youth Health. University of Auckland. Private Bag 92019 Wellesley Street, Auckland. Post Code 1142
Country 62648 0
New Zealand
Phone 62648 0
+64099236192
Fax 62648 0
+64093737486
Email 62648 0
cc.grant@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
No Results