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Trial registered on ANZCTR


Registration number
ACTRN12617001587392
Ethics application status
Approved
Date submitted
3/11/2017
Date registered
28/11/2017
Date last updated
24/10/2019
Date data sharing statement initially provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Prenatal screening for aneuploidy in the Australian Public Hospital System; a Non-Invasive Prenatal Screening Test (NIPT) feasibility study.
Scientific title
Prenatal screening for aneuploidy in the Australian Public Hospital System; a Non-Invasive Prenatal Screening Test (NIPT) feasibility study.
Secondary ID [1] 293261 0
None
Universal Trial Number (UTN)
Trial acronym
NIPT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aneuploidy 305310 0
Trisomy 21 (Down Syndrome) 305311 0
Trisomy 13 (Patau Syndrome) 305314 0
Trisomy 18 (Edwards Syndrome) 305315 0
Monosomy X (Turner Syndrome) 305316 0
Condition category
Condition code
Reproductive Health and Childbirth 304615 304615 0 0
Antenatal care
Human Genetics and Inherited Disorders 304681 304681 0 0
Down's syndrome
Human Genetics and Inherited Disorders 304682 304682 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
NIPT blood test

Intervention: NIPT blood test by trained staff in Perinatal Ultrasound Department, Web-based counselling through an iPAD not requiring a login. Face-to-face counselling
by a licenced genetic counsellor affiliated with the Perinatal Ultrasound Department at Nepean Hospital
All participants who undergo the NIPT test will undergo the NIPT blood test on one occasion.

Order: The NT bloods (PAPP-A and free beta-HCG will have been collected around 10 weeks of gestation in most patients that visit our unit). Patient will come in for NT (11w3d-13w6d) screening. Before their scan they will be asked to participate in the trial. If they agree, Written informed consent is obtained they will receive counselling (either face-to-face or on iPAD). After the counselling they will get to decide whether they want NT only of NIPT bloods collected as well. They will have the ultrasound and blood test for NIPT on the same day they have their genetic counselling in the Perinatal Ultrasound Department.

Secondary intervention: Participants will be randomly allocated to either face-to-face counselling or web-based counselling 12 minutes +/-. Both only performed on one occasion on the same day as the NT scan.
Location: Perinatal Ultrasound Department.

Counselling: Face-to-face counselling will be done by a licenced genetic counselling and will cover all the topics also covered in the counselling video.
Web-based: adaptation of: https://www.genea.com.au/genesyte-portal/patient/pre-video-questionnaire-complete

Brief description: *All face to face Genetic Counselling will be performed by an Associate Genetic Counsellor or Genetic Counsellor according to HGSA Guidelines for Genetic Counselling. Genetic Counselling is non-directional such that no advice is given about what the patient should do, rather an information session to consider all options.
*The consultation will cover the chance of chromosome anomalies based on age-related risk, what chromosomes are, the potential implications of a chromosome abnormality.
*Prenatal diagnosis options available (including all screening tests such as Combined First Trimester Screening, Nuchal Translucency alone and NIPT, all invasive tests: Chorionic Villus Sampling and amniocentesis, timing of results both for gestation and how long to results reporting).
*The limitations and benefits of each test will be discussed so that the patient is able to make an informed choice about which (if any) of the tests are best for her. The consultation will discuss the sensitivity and specificity of the testing for the major chromosome anomalies, risks of false positives, false negatives, and unreportable results.
*Reminder that patients can refuse any and all testing and should consider what she would do with an abnormal result.
*Considerations for the patient if the NIPT result is abnormal (recommendation to proceed to invasive testing via the Perinatal Ultrasound Dept. where care will be handled by the Specialist team). Advised that any abnormal results will be given by the Specialist team following the usual appropriate protocol at Nepean Hospital. Full discussions about the particular chromosome abnormality suspected will be discussed at the time of results.
*Considerations for the patient if the NIPT result is normal; ultrasound still recommended as per usual pregnancy care, chance of false negatives. Advised results will be communicated via phone by the Associate Genetic Counsellor.
*Contact details for the Associate Genetic Counsellor in case of any further questions/concerns.
*The web-based counselling will follow the identical format following a script using the same diagrams to help explain concepts.
Intervention code [1] 299520 0
Early detection / Screening
Comparator / control treatment
The control group is the face-to-face counselling
The intervention group is the web-based counselling.
Control group
Active

Outcomes
Primary outcome [1] 303846 0
The uptake of the NIPT within the Australian Public Hospital System.
How many patient opt to undergo NIPT out of our entire population presenting for first trimester NT screening.
Timepoint [1] 303846 0
12 months
Secondary outcome [1] 340265 0
Compare the overall cost to the healthcare system of offering NIPT as a first line screening test for Trisomy 21 to the current contingent model in detecting each correct diagnosis of Trisomy 21.
Analysis will include the detection rate of screening, results and outcomes as well as the cost per ‘correct’ result, taking into account extraneous factors such as additional need for further counselling for false positives, invasive procedures and losses due to invasive procedures. Results will be analysed by a Hospital linked statistician using Excel and SPSS software.
Timepoint [1] 340265 0
12 months
Secondary outcome [2] 340266 0
The effectiveness of different methods of genetic counselling (web-based compared to face-to-face) in providing appropriate education and support.

The learning effect will be analysed comparing the pre-counselling questionnaire to the post-counselling questionnaire. We will compare the learning effect between the two types of counselling methods.
Both pre-counselling and post-counselling questionnaires have been validated by a previous study (Lewis, C., et al., Development and validation of a measure of informed choice for women undergoing non-invasive prenatal testing for aneuploidy. Eur J Hum Genet, 2016. 24(6): p. 809-16.)
Timepoint [2] 340266 0
12 months.
The pre-counselling questionnaire will be provided to patients when they receive the information of the trial. The post-counselling questionnaire will be provided directly following the counselling.

Eligibility
Key inclusion criteria
All pregnant women, who have singleton pregnancy, aged 18 to 48, who are able to give informed consent, who are visiting the Nepean Hospital Perinatal Ultrasound Department and have been referred for their combined first trimester screening test for aneuploidy risk.
Minimum age
18 Years
Maximum age
48 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Multiple pregnancies
Aged under 18 or above 48 years.

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 not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
For the counselling method a dynamic random allocation methods will be used. Patient will be allocated to either face-to-face counselling or Web-based counselling depending on the day of the week their appointment has been scheduled.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The aim is to include 1000 participants to make an adequate estimation of the uptake of the NIPT in the Australian public hospital system. We will also be registering how many patients were offered participation in the trial.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/01/2018
Actual
27/03/2018
Date of last participant enrolment
Anticipated
30/04/2019
Actual
2/04/2019
Date of last data collection
Anticipated
Actual
Sample size
Target
1000
Accrual to date
Final
1000
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9326 0
Nepean Hospital - Kingswood
Recruitment postcode(s) [1] 17995 0
2747 - Kingswood

Funding & Sponsors
Funding source category [1] 297890 0
Commercial sector/Industry
Name [1] 297890 0
Illumina
Country [1] 297890 0
United States of America
Primary sponsor type
Hospital
Name
Nepean Hospital
Address
55 Derbystreet, Kingswood
NSW 2747
Sydney
Country
Australia
Secondary sponsor category [1] 296943 0
Commercial sector/Industry
Name [1] 296943 0
Illumina
Address [1] 296943 0
5200 Illumina Way (formerly 5200 Research Pl)
San Diego, CA 92122 USA
Country [1] 296943 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298939 0
Nepean Blue Mountains Human Research Ethics Committee
Ethics committee address [1] 298939 0
Level 5, South Block, Nepean Hospital
PO BOX 63, Penrith NSW 2751
Ethics committee country [1] 298939 0
Australia
Date submitted for ethics approval [1] 298939 0
08/11/2017
Approval date [1] 298939 0
01/03/2018
Ethics approval number [1] 298939 0

Summary
Brief summary
This study will offer the cell free fetal DNA blood test, NIPT, to all pregnant women visiting the Nepean Hospital Perinatal Ultrasound Department who have singleton pregnancies and have been referred for their combined first trimester screening test for Down syndrome risk. Once they have agreed to participate in the study, All will receive genetic counselling via either face-to-face consult or web-based education. The participants in the study will undergo their first trimester screening test, consisting of ultrasound and serum biochemistry, free ßHCG and PAPP-A, regardless of their choice to undergo NIPT. The NIPT will be offered to them free of charge. The aim is to include 1000 patients. The proposed time line is twelve months, with nine months of data collection and three months to complete analysis and write up results. The primary aim is to define the uptake of NIPT in the Australian Public Hospital system. A secondary aim is to compare the overall cost to the healthcare system of offering NIPT as a first line screening test for Trisomy 21 to the current contingent model in detecting each correct diagnosis of Trisomy 21. Analysis will include the detection rate of screening, results and outcomes as well as the cost per ‘correct’ result, taking into account extraneous factors such as additional need for further counselling for false positives, invasive procedures and losses due to invasive procedures. The efficacy of each protocol (NIPT versus the contingent model) using a dollar value per correct case detected, will also be determined. The tertiary aim will be to analysis the effectiveness of alternative methods of genetic counselling in providing appropriate education and support will be compared to the traditional face to face model.
Hypotheses to be tested:
That there will be a large uptake of NIPT within our population after either type of counselling.
That both traditional counselling as well as web based counselling will be effective counselling methods and will enable patients to make an informed decision regarding their first trimester screening.
That performing NIPT as the preferred method of screening for Down syndrome might be more cost effective to the public system compared to the current model.
Trial website
none
Trial related presentations / publications
none
Public notes

Contacts
Principal investigator
Name 78722 0
Prof Ron Benzie
Address 78722 0
Nepean Hospital, Perinatal Ultrasound Department
55 Derbystreet
NSW 2747 Kingswood

PO box 61
NSW 2751 Penrith
Country 78722 0
Australia
Phone 78722 0
+61247343163
Fax 78722 0
+61247343764
Email 78722 0
[email protected]
Contact person for public queries
Name 78723 0
Katie Ellis
Address 78723 0
Genea
2 King Street Deakin
ACT 2600 Canberra
Country 78723 0
Australia
Phone 78723 0
+61476 835 294
Fax 78723 0
Email 78723 0
[email protected]
Contact person for scientific queries
Name 78724 0
Nalayini Sathasivam
Address 78724 0
Nepean Hospital, Perinatal Ultrasound Department
55 Derbystreet
NSW 2747 Kingswood
Country 78724 0
Australia
Phone 78724 0
+61247341381
Fax 78724 0
Email 78724 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The combined first trimester results and obstetric data (mode of delivery, gestation)
Study protocol / consent form
When will data be available (start and end dates)?
Immediately following publication. No end date at this stage
Available to whom?
Researchers who provide a sound proposal and reason
Available for what types of analyses?
To achieve the aim in above proposal
How or where can data be obtained?
Proposals should be submitted to the current research team. The contact details are in the ANZCTR form (email [email protected]).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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No additional documents have been identified.