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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]

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)

Condition category

Condition code

Respiratory

Normal development and function of the respiratory system

Infection

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]

Prevention

Comparator / control treatment

Placebo. The placebo composition is based in coconut oil.

Control group

Placebo

Outcomes

Primary outcome [1]

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]

12 months after the enrollment of the child in the RCT.

Primary outcome [2]

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]

12 months after the enrollment of the child in the RCT.

Primary outcome [3]

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]

12 months after the enrollment of the child in the RCT.

Secondary outcome [1]

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]

12 months after the enrollment of the child in the RCT.

Secondary outcome [2]

Serum 25(OH)D concentration will be assessed at baseline and 6 months, plus at 12 months in a 10% subsample.

Timepoint [2]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/07/2016

Actual

Date of last participant enrolment

Anticipated

30/11/2017

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

300

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Cure Kids

Address [1]

Laundry Building. Suite 4, level 4. 58 Surrey Cresent. Grey Lynn. Post Code:1021. Auckland.

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Health and Disability Ethics Committee

Ethics committee address [1]

Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

23/03/2016

Approval date [1]

19/05/2016

Ethics approval number [1]

16/NTB/57

Ethics committee name [2]

Standing Committee on Therapeutic Trials (SCOTT).

Ethics committee address [2]

Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011

Ethics committee country [2]

New Zealand

Date submitted for ethics approval [2]

31/05/2016

Approval date [2]

Ethics approval number [2]

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

A/Prof Cameron Grant

Address

Department of Paediatrics: Child & Youth Health. University of Auckland. Private Bag 92019 Wellesley Street, Auckland. Post Code 1142

Country

New Zealand

Phone

+64099236192

Fax

+64093737486

[email protected]

Contact person for public queries

Name

Cameron Grant

Address

Department of Paediatrics: Child & Youth Health. University of Auckland. Private Bag 92019 Wellesley Street, Auckland Post Code 1142

Country

New Zealand

Phone

+64099236192

Fax

+64093737486

[email protected]

Contact person for scientific queries

Name

Cameron Grant

Address

Department of Paediatrics: Child & Youth Health. University of Auckland. Private Bag 92019 Wellesley Street, Auckland. Post Code 1142

Country

New Zealand

Phone

+64099236192

Fax

+64093737486

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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Documents added automatically

No additional documents have been identified.

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