Trisomy 21PEGASUSNCT01925742
Study of the Efficacy of New Non-invasive Prenatal Tests for Screening for Fetal Trisomies Using Maternal Blood
A study testing Integrated prenatal screening for Down's syndrome, Serum QUAD Assay for aneuploidy screening and Semiconductor MPSS NIPT assay using ccfDNA in maternal blood in people with Trisomy 21 and Trisomy 18, run by CHU de Quebec-Universite Laval at 5 sites in Canada.
Trial summary
Each year, 450,000 Canadian women become pregnant and, as a result of their participation in prenatal screening for Down syndrome, approximately 10,000 of them will have an amniocentesis (i.e. Read more about this study
- Who is it for?
- Ages 19 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Trisomy 21, Trisomy 18, Trisomy 13
- What is being tested?
- Integrated prenatal screening for Down's syndrome, Serum QUAD Assay for aneuploidy screening and Semiconductor MPSS NIPT assay using ccfDNA in maternal blood
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,819 participants
- Where
- 5 sitesCanada
- Study dates
- Nov 2013to Jun 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- women 19 years or older between 10 weeks and 23 weeks 6 days gestation undergoing amniocentesis or CVS for:
- positive prenatal screen;
- abnormal ultrasound
- previous pregnancy with trisomy
- patient or partner carrier of Robertsonian translocation involving chr 21
- positive NIPT result
- Maternal age 40 or more
- women 19 years and older who are 10 and 13 weeks 6 days gestation based on dating ultrasound (CRL) and are undergoing screening for Down syndrome (first trimester combined, SIPS or IPS)
Who cannot join
- women with multiple gestations
- women with twin demise (spontaneous or elective) at any gestational age
- women with active or history of malignancy
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
CHU Ste-Justine
Montreal, Quebec, H3T 1C5
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
CHU de Québec
Québec, Quebec, G1L3L5
Children's & Women's Health Centre
Vancouver, British Columbia, V6H 3N1
About this study
Official title: PEGASUS: PErsonalized Genomics for Prenatal Aneuploidy Screening USing Maternal Blood
Each year, 450,000 Canadian women become pregnant and, as a result of their participation in prenatal screening for Down syndrome, approximately 10,000 of them will have an amniocentesis (i.e. sampling of liquid surrounding the fetus) and of those, 315 will be found to carry a baby with Down syndrome and 70 normal pregnancies will be lost from complications of the procedure. It has been discovered recently that, during pregnancy, there is fetal DNA in maternal blood in sufficient quantities to be analysed and methods have been proposed to detect the presence or not of a fetus with Down syndrome using maternal blood. The introduction of genomic blood testing as proposed in the context of this project could lead to increased detection of Down syndrome, less invasive screening with 9700 amniocentesis avoided each year in Canada, improving the peace of mind of pregnant women, and preventing the accidental loss of 70 normal fetuses, at a lower overall cost than current practice. However, these methods still need to be validated before being appropriately introduced in routine care.
The study hypothesis is that new genomics-based non-invasive methods using fetal-DNA in maternal blood during pregnancy can be more effective than current prenatal screening methods for fetal aneuploidy.
This project will carry out an independent study that will validate the performance and utility of different new genomic technologies for screening in pregnant women using maternal blood. The team of researchers will compare the real-life performance of different non-invasive assays and strategies to screen for fetal aneuploidy, and identify an evidence-based cost-effective approach for implementation of this new technology in the Canadian health care system. The deliverables of this project will enable decision makers, pregnant women and their partner to make informed choices pertaining to prenatal genetic screening and diagnosis, such as screening for Down syndrome, and reduce the risk to pregnancies associated with amniocentesis.
Read the detailed description
The present study is a real life comparative effectiveness study that will compare the performances and costs of several prenatal screening modalities for fetal aneuploidy (see interventions).
- Conditions
- Trisomy 21, Trisomy 18, Trisomy 13
- Being tested
- Integrated prenatal screening for Down's syndrome, Serum QUAD Assay for aneuploidy screening, Semiconductor MPSS NIPT assay using ccfDNA in maternal blood, Optical-based MPSS NIPT assay using ccfDNA in maternal blood, Harmony™ Test (Ariosa Diagnostics)
- Keywords
- Fetal aneuploidy
- Medical subject headings
- Down Syndrome, Trisomy 18 Syndrome, Trisomy 13 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Integrated prenatal screening for Down's syndromeOther
Also called IPS, Prenatal serum screening, Aneuploidy screening, Down's syndrome screening
Analysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy.
Serum QUAD Assay for aneuploidy screeningOther
Also called First trimester QUAD prenatal screening assay
Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy
Semiconductor MPSS NIPT assay using ccfDNA in maternal bloodOther
Also called NIPD, MPSS, Non-invasive prenatal testing, Non-invasive prenatal diagnosis
Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay.
Optical-based MPSS NIPT assay using ccfDNA in maternal bloodOther
Also called NIPD, MPSS, Un-Targeted NIPD, Non-invasive prenatal testing
Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay.
Harmony™ Test (Ariosa Diagnostics)Other
Also called DANSR Assay
Test that is commercially available (Ariosa Diagnostics). (will be used for benchmarking purposes in a subset of each arm)
| Study group | Role | What they receive |
|---|---|---|
| Low Risk of aneuploidy | Experimental | Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) Receives: Other: Integrated prenatal screening for Down's syndrome; Other: Serum QUAD Assay for aneuploidy screening; Other: Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Other: Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Other: Harmony™ Test (Ariosa Diagnostics) |
| High risk of aneuploidy | Experimental | Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) (subset) Receives: Other: Integrated prenatal screening for Down's syndrome; Other: Serum QUAD Assay for aneuploidy screening; Other: Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Other: Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Other: Harmony™ Test (Ariosa Diagnostics) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of cases with Fetal trisomy 21, 18 or 13
Only pregnant women will be recruited, fetal outcome will be assessed by fetal karyotype or at or after delivery.
Measured: 6 weeks after the delivery date
Secondary outcomes (1)
Number of women with assay failure
Measured: At end of pregnancy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2013 (estimated)
- Study startNov 2013
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Trisomy 21Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,819 participants (actual)
Sponsor and investigators
- Lead sponsor
- CHU de Quebec-Universite Laval
- Sponsor type
- University, hospital or other
- Collaborators
- Laval University, Genome Canada, Genome Quebec, Genome British Columbia, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Francois Rousseau, MD MSc FRCPC, Principal investigator, Universite Laval and CHU de QuebecSylvie Langlois, MD FRCPC, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01925742
- Sponsor's protocol ID
- 2014-1236; SIRUL-102531
- Other IDs
- B13-06-1236
- Acronym
- PEGASUS
- Status last verified
- Apr 2016
- First submitted
- 16 Aug 2013
- Last updated
- 22 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Fibke C, Giroux S, Caron A, Starks E, Parker JDK, Swanson L, Jouan L, Langlois S, Rouleau G, Rousseau F, Karsan A. Effect of preexamination conditions in a centralized-testing model of non-invasive prenatal screening. Clin Chem Lab Med. 2021 Nov 11;60(2):183-190. doi: 10.1515/cclm-2021-0652. Print 2022 Jan 27.
PubMed 34761647Rousseau F, Langlois S, Johnson JA, Gekas J, Bujold E, Audibert F, Walker M, Giroux S, Caron A, Clement V, Blais J, MacLeod T, Moore R, Gauthier J, Jouan L, Laporte A, Diallo O, Parker J, Swanson L, Zhao Y, Labelle Y, Giguere Y, Forest JC, Little J, Karsan A, Rouleau G. Prospective head-to-head comparison of accuracy of two sequencing platforms for screening for fetal aneuploidy by cell-free DNA: the PEGASUS study. Eur J Hum Genet. 2019 Nov;27(11):1701-1715. doi: 10.1038/s41431-019-0443-0. Epub 2019 Jun 23.
PubMed 31231136
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PEGASUS: PErsonalized Genomics for Prenatal Aneuploidy Screening USing Maternal Blood
- ClinicalTrials.gov ID
- NCT01925742
- Acronym / sponsor ID
- PEGASUS / 2014-1236; SIRUL-102531
- Conditions
- Trisomy 21, Trisomy 18, Trisomy 13
- Keywords
- Fetal aneuploidy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,819 participants (actual)
- Lead sponsor
- CHU de Quebec-Universite LavalUniversity, hospital or other
- Collaborators
- Laval University, Genome Canada, Genome Quebec, Genome British Columbia, Canadian Institutes of Health Research (CIHR)
- Study start
- Nov 2013
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 20 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Each year, 450,000 Canadian women become pregnant and, as a result of their participation in prenatal screening for Down syndrome, approximately 10,000 of them will have an amniocentesis (i.e. sampling of liquid surrounding the fetus) and of those, 315 will be found to carry a baby with Down syndrome and 70 normal pregnancies will be lost from complications of the procedure. It has been discovered recently that, during pregnancy, there is fetal DNA in maternal blood in sufficient quantities to be analysed and methods have been proposed to detect the presence or not of a fetus with Down syndrome using maternal blood. The introduction of genomic blood testing as proposed in the context of this project could lead to increased detection of Down syndrome, less invasive screening with 9700 amniocentesis avoided each year in Canada, improving the peace of mind of pregnant women, and preventing the accidental loss of 70 normal fetuses, at a lower overall cost than current practice. However, these methods still need to be validated before being appropriately introduced in routine care.
The study hypothesis is that new genomics-based non-invasive methods using fetal-DNA in maternal blood during pregnancy can be more effective than current prenatal screening methods for fetal aneuploidy.
This project will carry out an independent study that will validate the performance and utility of different new genomic technologies for screening in pregnant women using maternal blood. The team of researchers will compare the real-life performance of different non-invasive assays and strategies to screen for fetal aneuploidy, and identify an evidence-based cost-effective approach for implementation of this new technology in the Canadian health care system. The deliverables of this project will enable decision makers, pregnant women and their partner to make informed choices pertaining to prenatal genetic screening and diagnosis, such as screening for Down syndrome, and reduce the risk to pregnancies associated with amniocentesis.
Detailed description
The present study is a real life comparative effectiveness study that will compare the performances and costs of several prenatal screening modalities for fetal aneuploidy (see interventions).
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low Risk of aneuploidy | Experimental | Other: Integrated prenatal screening for Down's syndrome, Other: Serum QUAD Assay for aneuploidy screening, Other: Semiconductor MPSS NIPT assay using ccfDNA in maternal blood, Other: Optical-based MPSS NIPT assay using ccfDNA in maternal blood, Other: Harmony™ Test (Ariosa Diagnostics)Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) |
| High risk of aneuploidy | Experimental | Other: Integrated prenatal screening for Down's syndrome, Other: Serum QUAD Assay for aneuploidy screening, Other: Semiconductor MPSS NIPT assay using ccfDNA in maternal blood, Other: Optical-based MPSS NIPT assay using ccfDNA in maternal blood, Other: Harmony™ Test (Ariosa Diagnostics)Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) (subset) |
Who may qualify
- Ages
- 19 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- women 19 years or older between 10 weeks and 23 weeks 6 days gestation undergoing amniocentesis or CVS for:
- positive prenatal screen;
- abnormal ultrasound
- previous pregnancy with trisomy
- patient or partner carrier of Robertsonian translocation involving chr 21
Key exclusion criteria (3 listed)
- women with multiple gestations
- women with twin demise (spontaneous or elective) at any gestational age
- women with active or history of malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Integrated prenatal screening for Down's syndromeAlso: IPS, Prenatal serum screening, Aneuploidy screening, Down's syndrome screeningAnalysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy. | Other | High risk of aneuploidy, Low Risk of aneuploidy |
| Serum QUAD Assay for aneuploidy screeningAlso: First trimester QUAD prenatal screening assaySeries of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy | Other | High risk of aneuploidy, Low Risk of aneuploidy |
| Semiconductor MPSS NIPT assay using ccfDNA in maternal bloodAlso: NIPD, MPSS, Non-invasive prenatal testing, Non-invasive prenatal diagnosisAnalysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay. | Other | High risk of aneuploidy, Low Risk of aneuploidy |
| Optical-based MPSS NIPT assay using ccfDNA in maternal bloodAlso: NIPD, MPSS, Un-Targeted NIPD, Non-invasive prenatal testingAnalysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay. | Other | High risk of aneuploidy, Low Risk of aneuploidy |
| Harmony™ Test (Ariosa Diagnostics)Also: DANSR AssayTest that is commercially available (Ariosa Diagnostics). (will be used for benchmarking purposes in a subset of each arm) | Other | High risk of aneuploidy, Low Risk of aneuploidy |
Primary outcome
Number of cases with Fetal trisomy 21, 18 or 13
Time frame: 6 weeks after the delivery date
Only pregnant women will be recruited, fetal outcome will be assessed by fetal karyotype or at or after delivery.
1 secondary outcome
Number of women with assay failure
Time frame: At end of pregnancy.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2018.
- Derived from this study: PubMed 34761647Fibke C, Giroux S, Caron A, Starks E, Parker JDK, Swanson L, Jouan L, Langlois S, Rouleau G, Rousseau F, Karsan A. Effect of preexamination conditions in a centralized-testing model of non-invasive prenatal screening. Clin Chem Lab Med. 2021 Nov 11;60(2):183-190. doi: 10.1515/cclm-2021-0652. Print 2022 Jan 27.
- Derived from this study: PubMed 31231136Rousseau F, Langlois S, Johnson JA, Gekas J, Bujold E, Audibert F, Walker M, Giroux S, Caron A, Clement V, Blais J, MacLeod T, Moore R, Gauthier J, Jouan L, Laporte A, Diallo O, Parker J, Swanson L, Zhao Y, Labelle Y, Giguere Y, Forest JC, Little J, Karsan A, Rouleau G. Prospective head-to-head comparison of accuracy of two sequencing platforms for screening for fetal aneuploidy by cell-free DNA: the PEGASUS study. Eur J Hum Genet. 2019 Nov;27(11):1701-1715. doi: 10.1038/s41431-019-0443-0. Epub 2019 Jun 23.
Related trials for Trisomy 21
Active, not recruitingPhase 3
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma
Not yet recruiting
Executive Function Play Opportunities for Children With Down Syndrome
Down Syndrome, Trisomy 21
RecruitingObservational study
Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy
Down Syndrome
Not yet recruitingObservational study
Hematological Profile in Children With Numerical Chromosomal Disorders
Down Syndrome, Turner Syndrome
Not yet recruiting
Single Session Support for Parents of Children With Neurodevelopmental Disabilities Struggling With Anxious Avoidance
Neurodevelopmental Disorders, Autism Spectrum Disorder (ASD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francois Rousseau, MD MSc FRCPC principal investigator
Universite Laval and CHU de Quebec
Sylvie Langlois, MD FRCPC principal investigator
University of British Columbia
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Integrated prenatal screening for Down's syndrome, Serum QUAD Assay for aneuploidy screening and Semiconductor MPSS NIPT assay using ccfDNA in maternal blood in people with Trisomy 21 and Trisomy 18, run by CHU de Quebec-Universite Laval at 5 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of cases with Fetal trisomy 21, 18 or 13 (time frame: 6 weeks after the delivery date). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01925742, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2018.