Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001370998
Ethics application status
Approved
Date submitted
26/10/2020
Date registered
21/12/2020
Date last updated
4/08/2022
Date data sharing statement initially provided
21/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Children's Inpatient Research Collaboration of Australia and New Zealand (CIRCAN) OM85 trial
Scientific title
Impact of the immunomodulator OM85 on wheeze-associated hospitalisation in preschoolers: a multi-centre, randomised, double-blind, placebo-controlled trial
Secondary ID [1] 302417 0
ARROW Trial
Universal Trial Number (UTN)
U1111-1258-8111
Trial acronym
Children's inpatient collaboration of Australia and New Zeland (CIRCAN) OM85 Trial
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
recurrent wheeze 319212 0
Condition category
Condition code
Respiratory 317182 317182 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The aim of this study is to assess the efficacy of OM-85 for prevention of hospital admission in preschool aged children with recurrent wheeze in comparison to placebo.

Half the participants will be given capsules containing OM-85 (Broncho-Vaxom), half will be given a placebo.
- the dose administered = 3.5mg daily;
- the duration of administration =first 10 days of the calendar month for 12 months;
- the mode of administration = oral tablet.
Excipients of the capsule include (pregelatinised) corn starch, magnesium stearate, sodium glutamate (E621), mannitol, gelatin, antioxidant: propyl gallate (E310), colour, indigotine (E132).

Adherence will be monitors via self reporting in the electronic diaries every 10 days. Participants may be called to continue engagement, to check adverse events, to encourage them to complete the diaries and check on the status of their study capsules.
Intervention code [1] 318699 0
Prevention
Comparator / control treatment
Placebo, containing all the ingredients of the treatment without the bacterial products.
Excipients of the capsule include (pregelatinised) corn starch, magnesium stearate, sodium glutamate (E621), mannitol, gelatin, antioxidant: propyl gallate (E310), colour, indigotine (E132).

- the duration of administration =first 10 days of the calendar month for 12 months;
- the mode of administration = oral tablet.

Adherence will be monitors via self reporting in the electronic diaries every 10 days. Participants may be called to continue engagement, to check adverse events, to encourage them to complete the diaries and check on the status of their study capsules.
Control group
Placebo

Outcomes
Primary outcome [1] 325258 0
To determine the efficacy of OM-85 for prevention of hospital admission due to an acute wheezing illness in preschool aged children with recurrent wheeze compared with placebo.

Hospital admission will be assessed by an electronic diary the participant fills in every 10 days. Where necessary the patient medical records will be queried
Timepoint [1] 325258 0
12 months post commencement of treatment
Secondary outcome [1] 387355 0
To assess the effect of OM-85 on subsequent recurrent wheeze events in preschool aged children with reference to number, severity and duration of wheeze episodes.

Outcome will be assessed by an electronic diary the participant fills in every 10 days. Where necessary the patient medical records will be queried
Timepoint [1] 387355 0
12 months post commencement of treatment
Secondary outcome [2] 389277 0
To assess the effect of OM-85 on subsequent recurrent wheeze events in preschool aged children with reference to quality of life.

Outcome will be assessed by an electronic diary the participant fills in every 10 days. Where necessary the patient medical records will be queried
Timepoint [2] 389277 0
12 months from commencement of treatment
Secondary outcome [3] 389278 0
To assess the effect of OM-85 on subsequent recurrent wheeze events in preschool aged children with reference to health resource utilisation, lost productivity, and cost-effectiveness.

Outcome will be assessed by an electronic diary the participant fills in every 10 days. Where necessary the patient medical records will be queried. Health resource utilisation (hospital, community, general practice) will be reported as the mean number of HRU per child over a 12 month period . Parent/guardian loss of productivity (days of work missed / days out of role) will be preported at the mean number days lost over a 12 month period.

The measured health service use will be valued using national unit costs, such as National Efficient Price for hospital admission (weighted by length of stay as applicable) and Medicare published rebate levels for community health services and pharmaceuticals. The secondary economic analysis will assess the impact of the intervention on families (including parent-reported out-of-pocket costs, productivity impacts (days of paid work missed/days out of unpaid role) and quality of life outcomes) through a cost-consequences analysis from a societal perspective that compares impact of OM-85 on all measured outcomes to the difference in all costs (to health system, work and family).
Timepoint [3] 389278 0
12 months from commencement of study

Eligibility
Key inclusion criteria
1. Male or female children age 1 to 5.99 years who in the preceding 12 months have had: at least one hospital presentation lasting more than 4 hours and at least 2 other wheeze episodes and requiring repeated administration of an inhaled bronchodilator.
2. Parent(s) or legal guardian(s) of the child is able to understand the study requirements and willing to provide informed consent
Minimum age
1 Years
Maximum age
6 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known adverse reaction or hypersensitivity to bacterial lysates or to any of the excipients in OM-85 in accordance with the composition.
2. Anatomic alterations of the respiratory tract.
3. Chronic respiratory diseases other than preschool wheeze/asthma. These include chronic suppurative lung disease, and chronic lung disease of prematurity, defined by a persisting oxygen requirement at a corrected gestation age of 40 weeks.
4. History of malignancy, autoimmune disease, liver or kidney failure.
5. Treatment with immunosuppressant drugs including methotrexate, cyclosporine or azathioprine within 30 days prior to enrolment in this study.

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)
The randomisation schedule will be computer generated by an independent statistician using block randomisation, The schedule will be sent to the central pharmacist at the who will prepare the study drugs labelled with just the study number
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will be computer generated by an independent statistician using block randomisation, with variable block sizes, stratified by <2 versus >=2 admissions for wheeze in the preceding 12 months(including the index admission), and age<3 years or >=3 years.

The schedule will be sent to a central pharmacist who will prepare the study drugs labelled with just the study number. Once a participant is ready for randomisation, they will be allocated the next available study number in their strata which will correspond to a bottle of study drug. The study medication will be couriered from the Pharmacy directly to the participants home.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size: The most recent published estimates and analysis of local hospital records indicate an annual readmission rate for preschool wheeze of over 20%.
The study is powered to identify a reduction in this rate by 25%, which the CIRCAN paediatricians identified as the minimum effect size required to change their current practice. In order to have 80% power to identify a reduction from 20% readmission over 12 months in the placebo group to 15% in the OM-85 group (using a two-sided chi-squared test with alpha=0.05), we require 945 per group. In order to allow for a 20% loss to follow up we aim to recruit a total of 2268 participants.

Data will be collected to meet the CONSORT guidelines for reporting of randomised trials, including data on eligible non-participants. Analyses will be conducted according to the intention-to-treat principle with participants analysed according to the intervention they were allocated to. The primary outcome, will be compared between the groups using logistic regression adjusted for <2 versus >=2 admissions for wheeze in the preceding 12 months and age<3 years or >=3 years as used in stratification of the randomisation. Results will be reported as an (adjusted) odds ratio, 95% CI and the corresponding p-value.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/03/2021
Actual
1/04/2022
Date of last participant enrolment
Anticipated
31/03/2024
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
2268
Accrual to date
45
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 17659 0
Albury Wodonga Health - Albury campus - Albury
Recruitment hospital [2] 17660 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 17661 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment hospital [4] 17662 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [5] 17663 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [6] 17664 0
Bundaberg Hospital - Bundaberg
Recruitment hospital [7] 17665 0
Box Hill Hospital - Box Hill
Recruitment hospital [8] 17666 0
Angliss Hospital - Upper Ferntree Gully
Recruitment hospital [9] 17667 0
Maroondah Hospital - Ringwood East
Recruitment hospital [10] 17668 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [11] 17669 0
Perth Children's Hospital - Nedlands
Recruitment hospital [12] 17670 0
Gosford Hospital - Gosford
Recruitment hospital [13] 17671 0
Wyong Public Hospital - Hamlyn Terrace
Recruitment hospital [14] 17672 0
John Hunter Hospital - New Lambton
Recruitment hospital [15] 17673 0
Monash Children’s Hospital - Clayton
Recruitment hospital [16] 17674 0
Dandenong Hospital - Dandenong
Recruitment hospital [17] 17675 0
Casey Hospital - Berwick
Recruitment hospital [18] 17676 0
The Northern Hospital - Epping
Recruitment hospital [19] 17677 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [20] 17678 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [21] 17679 0
Redland Hospital - Cleveland
Recruitment hospital [22] 17680 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [23] 17681 0
Royal Hobart Hospital - Hobart
Recruitment hospital [24] 17682 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [25] 17683 0
St George Hospital (QLD) - St George
Recruitment hospital [26] 17684 0
Sunshine Hospital - St Albans
Recruitment hospital [27] 17685 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [28] 17686 0
Werribee Mercy Hospital - Werribee
Recruitment hospital [29] 17687 0
Wollongong Hospital - Wollongong
Recruitment hospital [30] 17688 0
Shoalhaven Hospital - Nowra
Recruitment postcode(s) [1] 31505 0
2640 - Albury
Recruitment postcode(s) [2] 31506 0
3084 - Heidelberg
Recruitment postcode(s) [3] 31507 0
3350 - Ballarat Central
Recruitment postcode(s) [4] 31508 0
3220 - Geelong
Recruitment postcode(s) [5] 31509 0
3550 - Bendigo
Recruitment postcode(s) [6] 31510 0
4670 - Bundaberg
Recruitment postcode(s) [7] 31511 0
3128 - Box Hill
Recruitment postcode(s) [8] 31512 0
3156 - Upper Ferntree Gully
Recruitment postcode(s) [9] 31513 0
3135 - Ringwood East
Recruitment postcode(s) [10] 31514 0
6150 - Murdoch
Recruitment postcode(s) [11] 31515 0
6009 - Nedlands
Recruitment postcode(s) [12] 31516 0
2250 - Gosford
Recruitment postcode(s) [13] 31517 0
2259 - Hamlyn Terrace
Recruitment postcode(s) [14] 31518 0
2305 - New Lambton
Recruitment postcode(s) [15] 31519 0
3168 - Clayton
Recruitment postcode(s) [16] 31520 0
3175 - Dandenong
Recruitment postcode(s) [17] 31521 0
3806 - Berwick
Recruitment postcode(s) [18] 31522 0
3076 - Epping
Recruitment postcode(s) [19] 31523 0
4101 - South Brisbane
Recruitment postcode(s) [20] 31524 0
3052 - Parkville
Recruitment postcode(s) [21] 31525 0
4163 - Cleveland
Recruitment postcode(s) [22] 31526 0
0810 - Tiwi
Recruitment postcode(s) [23] 31527 0
7000 - Hobart
Recruitment postcode(s) [24] 31528 0
2065 - St Leonards
Recruitment postcode(s) [25] 31529 0
4487 - St George
Recruitment postcode(s) [26] 31530 0
3021 - St Albans
Recruitment postcode(s) [27] 31531 0
2145 - Westmead
Recruitment postcode(s) [28] 31532 0
3030 - Werribee
Recruitment postcode(s) [29] 31533 0
2500 - Wollongong
Recruitment postcode(s) [30] 31534 0
2541 - Nowra
Recruitment outside Australia
Country [1] 23019 0
New Zealand
State/province [1] 23019 0
all

Funding & Sponsors
Funding source category [1] 306713 0
Government body
Name [1] 306713 0
National Health and Medical Research Council
Country [1] 306713 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
1 Gheringhap Street, Geelong Victoria 3220
Country
Australia
Secondary sponsor category [1] 307261 0
University
Name [1] 307261 0
University of Auckland
Address [1] 307261 0
24 Princes Street, Alfred Nathan House, Auckland Auckland Region 1142
Country [1] 307261 0
New Zealand
Other collaborator category [1] 281491 0
Hospital
Name [1] 281491 0
The Royal Children's Hospital, Melbourne
Address [1] 281491 0
50 Flemington Street, Parkville Victoria 3052
Country [1] 281491 0
Australia
Other collaborator category [2] 281492 0
Hospital
Name [2] 281492 0
Murdoch Children's Research Institute
Address [2] 281492 0
Flemington Road, Parkville Victoria 3052 Australia
Country [2] 281492 0
Australia
Other collaborator category [3] 281493 0
University
Name [3] 281493 0
University of Queensland
Address [3] 281493 0
St Lucia, Brisbane Queensland 4072
Country [3] 281493 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306883 0
The Royal Children's Hospital, Melbourne
Ethics committee address [1] 306883 0
Ethics committee country [1] 306883 0
Australia
Date submitted for ethics approval [1] 306883 0
29/01/2021
Approval date [1] 306883 0
30/09/2021
Ethics approval number [1] 306883 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105338 0
Prof Peter Vuillermin
Address 105338 0
Child Health Research Unit,
University Hospital Geelong
PO Box 281
VIC 3220
Country 105338 0
Australia
Phone 105338 0
+61 0400071218
Fax 105338 0
Email 105338 0
[email protected]
Contact person for public queries
Name 105339 0
Nicola Cooley
Address 105339 0
Child Health Research Unit,
University Hospital Geelong
PO Box 281
VIC 3220
Country 105339 0
Australia
Phone 105339 0
+61 03 4215 3389
Fax 105339 0
Email 105339 0
[email protected]
Contact person for scientific queries
Name 105340 0
Peter Vuillermin
Address 105340 0
Child Health Research Unit,
University Hospital Geelong
PO Box 281
VIC 3220
Country 105340 0
Australia
Phone 105340 0
+61 0400071218
Fax 105340 0
Email 105340 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.