PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood (PEGASUS-2)

Laval University

Status: Active, not recruiting

Conditions: Aneuploidy; Prenatal Disorder

Treatments: Diagnostic Test: Traditional integrated prenatal screening; Diagnostic Test: Second-tier Non-invasive prenatal screening (NIPS); Diagnostic Test: First-tier Non-invasive prenatal screening (NIPS); Diagnostic Test: Invasive prenatal testing for fetal aneuploidy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03831256

SIRUL 118984

Details and patient eligibility

About

This project aims to provide high- quality evidence to inform decisions by health care organisations about using first-tier non-invasive prenatal screening (NIPS) to replace traditional screening tests for trisomy 21, and potentially to screen for other fetal chromosome anomalies. We will compare the current screening approach of second-tier NIPS with the use of first-tier NIPS in a large cohort of pregnant women.

Full description

There is some data on the performance of NIPS as a first tier screening test but our systematic review has shown that no trial comparing the effectiveness (utility) of 2nd-tier NIPS with that of first-tier NIPS has been published . Further it is important for health care decision makers to have evidence produced in Canada since the geographical context of healthcare can affect uptake as well as patient decision and thus their healthcare trajectories. There is a need for a trial that is between an explanatory trial and a pragmatic trial to provide the types of answer that we aim to document in the present state of knowledge on NIPS-based screening strategies in Canada. Our Objective is to perform a pan-Canadian large-scale comparative utility (clinical outcomes) study of first-tier NIPS (expanded or not) as compared to the new standard of care (NIPS as a 2nd tier test performed much later during pregnancy and only in high risk pregnancies).

Enrollment: 7,849 patients

Sex: Female

Ages: 19+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Pregnant women 19 years or older wanting prenatal screening
• 10-13+6 wks determined by dating ultrasound or last menstrual period.
• Not intending to pursue self pay NIPT

Exclusion criteria

• Known fetal anomaly at the time of recruitment
• Multiple gestation
• Known twin demise
• Planned CVS or amnio for known genetic condition.

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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7,849 participants in 2 patient groups

Standard of care (2nd tier NIPS)

Active Comparator group

Description:

For the standard-of-care arm (2nd tier NIPS) women will undergo Traditional integrated prenatal screening i.e. traditional biochemical (+/- NT) and those with a positive screen for T21 or T18 will be offered Second-tier Non-invasive prenatal screening (NIPS) (for T21, T18, T13) or Invasive prenatal testing for fetal aneuploidy. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).

Treatment:

Diagnostic Test: Invasive prenatal testing for fetal aneuploidy

Diagnostic Test: Second-tier Non-invasive prenatal screening (NIPS)

Diagnostic Test: Traditional integrated prenatal screening

First-tier NIPS

Experimental group

Description:

For the intervention arm (1st tier NIPS) women will receive First-tier Non-invasive prenatal screening (NIPS) i.e. provide a blood sample between 10-13+5 weeks gestation with NIPS results within 7 - 10 days of sample collection. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. In case of a failed NIPS test (expected to be between 2% and 4% of samples), a new blood sample will be drawn for NIPS retest as well as for a traditional SIPS(serum integrated prenatal screening) or QUAD(quadruple marker prenatal screening) screen (depending on gestational age). Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).

Treatment:

Diagnostic Test: Invasive prenatal testing for fetal aneuploidy

Diagnostic Test: First-tier Non-invasive prenatal screening (NIPS)