ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12621000484842

Ethics application status

Approved

Date submitted

9/02/2021

Date registered

26/04/2021

Date last updated

26/04/2021

Date data sharing statement initially provided

26/04/2021

Type of registration

Retrospectively registered

Titles & IDs

Public title

Targeted Screening for Congenital Cytomegalovirus-related Hearing loss in infants in Western Australia

Scientific title

Targeted Screening for Congenital Cytomegalovirus-related Hearing loss in infants up to 14 days old in Western Australia

Secondary ID [1]

Funding body: Award reference: 2019_CG_Kuthubutheen

Universal Trial Number (UTN)

U1111-1264-8031

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Congenital CMV-related Hearing Loss

Condition category

Condition code

Ear

Deafness

Infection

Other infectious diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Targeted testing of infants for congenital cytomegalovirus (cCMV).
Infants are targeted using the newborn hearing screen result.
Infants who fail ('refer') on newborn hearing screening are at increased risk of cCMV and (their parents/guardians) will be contacted to offer enrolment in the study - and testing for cCMV.
Currently testing is not routinely offered at this time point.
All infants in the state (meeting eligibility criteria) will be offered enrolment.
cCMV testing (saliva and urine) protocols in the study are the same as those used by the pathology centre and each request form is attached to a 'standard operating procedure' (SOP) instruction sheet approved by this centre.
The difference in the study is the testing time point, the methods of sampling and testing are standard.
Parents/guardians of the infant attend a community or hospital pathology centre (at the most convenient location for the family) which has been supplied with the request form and SOP. The pathology centre staff take a buccal swab from the infant (1 minute to complete) and the sample is processed in the standard manner. Study doctor/nurse inform the parents of the result. If this is negative the infant is discharged from the study. If it is positive, the infant again attends a pathology centre for confirmation of this via urine testing (nappy with cotton wool or specimen jar) which a gold standard testing protocol (if wet nappy, can taken within 1 minute, if not await wet nappy - usually less than 1 hour).
Study staff inform the family of the result, which if negative results in discharge from the study, if positive the usual care pathway (Audiology testing, ENT, Infectious diseases, Ophthalmology) is activated and expedited.
There are no further requirements from the infant and their family besides the saliva and urine testing, apart from access to the infants medical records which are reviewed for the duration of the (2 year) study to assess their clinical outcomes, in the cases of cCMV positive infants only.

The study staff assess testing attendance as every result is followed up - indicating willingness to participate. Additional investigative and treatment decision-making for cCMV positive infants is observed only.

Intervention code [1]

Early detection / Screening

Comparator / control treatment

No control

Control group

Uncontrolled

Outcomes

Primary outcome [1]

To assess whether targeted congenital cytomegalovirus testing is able to be completed by day 21 of life in Infants at high-risk of the virus across Western Australia

Used to assess this:
The proportion of infants unable to be recruited due to delayed NBHS testing/delayed communication of these results/unable to contact the parents or guardians by day 14 of life/infants who do not attend testing centres despite being enrolled

The electronic hospital results platform is used to determine attendance

Timepoint [1]

Reported cCMV result by day 21 of life

Secondary outcome [1]

To determine the incidence of congenital CMV (cCMV) infection in those infants who fail their newborn hearing screen in WA

The proportion of enrolled infants with a positive cCMV saliva and urine sample as a proportion of all infants tested is the measure of incidence

Timepoint [1]

Cumulative testing data will be assessed at 6 months, 1 year and at the conclusion of the 2 year study

Secondary outcome [2]

The proportion of participants not tested by day 21 of life as assessed via audit of patient electronic results platform

Timepoint [2]

Cumulative testing data will be assessed at 6 months, 1 year and at the conclusion of the 2 year study

Secondary outcome [3]

To determine the proportion of early diagnoses that result in time-critical treatment being administered as assessed via audit of the study database

Timepoint [3]

Cumulative testing data will be assessed at 6 months, 1 year and at the conclusion of the 2 year study

Secondary outcome [4]

Access has been approved by the hospital ethics committee and is explicitly stated during consent, to access the participants' medical records to determine the clinical progression of study participants during the study: including patterns of hearing loss, speech and language development and the meeting of other developmental milestones

Timepoint [4]

Cumulative testing data will be assessed at 6 months, 1 year and at the conclusion of the 2 year study

Eligibility

Key inclusion criteria

During the 2 year study
1. all infants born in Western Australia undergoing newborn hearing screening which results in a 'refer' (fail) result in one or both ears
2. Are age less than day 11 for rural/remote infants and day 14 for infants in metropolitan area on the day the 'refer' result is received by the study team
3. Has a legally acceptable representative able to provide informed consent on behalf of the infant

Minimum age

No limit

Maximum age

14 Days

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Newborn hearing screen ‘refer’ result but infant aged over 11 days of age (rural/remote participants) and 14 days of age (metropolitan participant)
2. Medically unwell – although not specifically excluded from the study some Infants may be too unwell to reasonably take part. In consultation with the treating team, the research team would consider the appropriateness of approaching the guardians.
3. Lack of a legally acceptable representative able to provide informed consent on behalf of the infant.

Study design

Purpose of the study

Diagnosis

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation is not concealed

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

The number of eligible participants based on the WA annual birth rate and 2% ‘refer’ rate would equate 700 annual NBHS ‘refers’. Assuming an 80% enrolment rate we estimate that 560 referred babies per year will proceed to be swabbed. Assuming also, a conservative 2% rate of hearing loss attributable to cCMV in those who are swabbed, we expect to identify 11 cCMV patients out of approximately 560 participating referrals per year. Over the 2 year study period we would therefore expect to be able to estimate the incidence rate of congenital CMV infection in those who fail their NBHS with a margin of error of 1.7%, where the margin of error here is half of the 95% confidence interval width. The margin of error will be approximately 2% if only 600 swabs are obtained, say, for example, if recruitment was slower than expected or stopped after about 18 months. A Biostatistician has been consulted in relation to the power of the study.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

2/11/2020

Date of last participant enrolment

Anticipated

7/11/2022

Actual

Date of last data collection

Anticipated

7/12/2022

Actual

Sample size

Target

140

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Perth Children's Hospital - Nedlands

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

the Garnett-Passe Foundation

Address [1]

Suite 2.06, 517-535 Flinders Lane
Melbourne VIC 3000

Country [1]

Australia

Primary sponsor type

Individual

Name

Dr Jafri Kuthubutheen

Address

Perth Childrens Hospital, 15 Hospital Avenue Nedlands, Western Australia, 6009

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

Perth Childrens Hospital

Address [1]

Perth Childrens Hospital, 15 Hospital Avenue Nedlands, Western Australia 6009

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Child and Adolescent Health Service: Human research Ethics Committee

Ethics committee address [1]

Perth Children's Hospital
Level 5, Office 5E
15 Hospital Avenue
Nedlands, WA, 6009

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

13/10/2020

Ethics approval number [1]

RGS3073

Summary

Brief summary

Aim(s):
This project aims to examine the feasibility of establishing a state-wide screening program in WA to detect congenital CMV-related hearing loss in high-risk infants. The project does not aim to determine if early treatments are effective, this is outside of the scope of the study.  
 
Primary Objectives:
 1.    To determine the incidence of congenital CMV infection in those infants who fail their newborn hearing screen in WA
 
2.    To monitor the clinical progression of these patients/participants over time and their patterns of hearing loss to be able to better understand the disease in WA
 
Secondary objectives:

1.    a) To identify and address potential barriers to early detection of cCMV (less than 21 days) in order to facilitate feasible (cost-effective, minimally invasive) diagnosis via a saliva swab
 b) To determine whether early diagnosis has the potential to make time-critical treatment possible (within 30 days).
 
2.    If targeted testing is found to be feasible - to create and implement a protocol which forms a clinical pathway for targeted testing of infants at high-risk of cCMV in WA.
 
Hypothesis: 
We hypothesise that timely targeted cCMV screening is both important and feasible to implement into WA Newborn Hearing Screening Guidelines.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Jafri Kuthubutheen

Address

Ear, nose and Throat Department
Perth Children's Hospital
15 Hospital Ave, Nedlands WA 6009

Country

Australia

Phone

+61401679302

Fax

[email protected]

Contact person for public queries

Name

Allison Reid

Address

Ear, nose and Throat Department
Perth Children's Hospital
15 Hospital Ave, Nedlands WA 6009

Country

Australia

Phone

+61 08 6456 2222

Fax

[email protected]

Contact person for scientific queries

Name

Allison Reid

Address

Ear, nose and Throat Department
Perth Children's Hospital
15 Hospital Ave, Nedlands WA 6009

Country

Australia

Phone

+61 08 6456 2222

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Aggregated data will be available.
Individual participant data will not due to relatively limited numbers of positives expected and that these patients may be identifiable (even to themselves) because of this.

What supporting documents are/will be available?

Doc. No.	Type	Email	Attachment
10523	Study protocol	[email protected]
10524	Ethical approval	[email protected]	381390-(Uploaded-09-02-2021-15-08-34)-Study-related document.pdf
10525	Informed consent form	[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Congenital cytomegalovirus: the case for targeted infant screening in Australia.	2022	https://dx.doi.org/10.5694/mja2.51406

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically