Down SyndromeSAFE 21NCT02127515
Non Invasive Prenatal Testing of Down Syndrome
A study testing Non Invasive Prenatal Testing and Invasive Prenatal Testing in people with Down Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
This is a randomized controlled trial in women at risk following combined prenatal screening for Down Syndrome. Women will be asked about their preferences between NIPT and routine prenatal diagnosis based on a dedicated questionnaire. Women will then be randomized between NIPT and standard invasive prenatal diagnosis. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Down Syndrome
- What is being tested?
- Non Invasive Prenatal Testing and Invasive Prenatal Testing
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,111 participants
- Where
- 1 siteFrance
- Study dates
- 8 Apr 2014to 7 Nov 2016
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- pregnant women over 18
- at risk for Down syndrome> 1/250 based on combined screening using ultrasound together with maternal serum markers and prior to fetal karyotyping
- singleton pregnancy
- pregnancy between 11SA et 18SA
- willing a fetal karyotype
Who cannot join
- risk for Down syndrome< 1/250 or >1/5
- NT> 3 mm, PAPP-A or beta HCG <0.3 MoM or >5 MoM
- multiple pregnancy , vanishing twin
- morphological abnormalities at US
- Kown chromosomal anomaly in parents
- Patients not willing a fetal karyotype
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Non Invasive Prenatal Testing of Down Syndrome From Maternal Blood Sample
This is a randomized controlled trial in women at risk following combined prenatal screening for Down Syndrome. Women will be asked about their preferences between NIPT and routine prenatal diagnosis based on a dedicated questionnaire. Women will then be randomized between NIPT and standard invasive prenatal diagnosis.
Read the detailed description
This is a randomized controlled trial in women at risk following combined prenatal screening for Down Syndrome. Women will be asked about their preferences between NIPT and routine prenatal diagnosis based on a dedicated questionnaire. Women will then be randomized between NIPT and standard invasive prenatal diagnosis.
The general objectives are :
- Promote the rapid and large implementation of Non Invasive Prenatal Testing (NIPT) for Down syndrome.
- Improve the management of women at risk after combined first trimester screening and reduce the number of invasive procedures and induced miscarriages .
- Evaluate NIPT medically (in reducing the rate of invasive sampling and related complications, diagnostic performance and feasibility and acceptability in routine practice) and based on cost-analysis in comparison with standard invasive prenatal diagnosis currently proposed .
- Clarify the conditions of implementation and dissemination of NIPT in the overall organization of prenatal screening for trisomy 21 (and provide data to later adjust or not the combination of tests and thresholds).
Promote the organization as networks of professionals involved in prenatal screening for trisomy 21 in order to allow the emergence of a national system of collection of outcomes to improve the quality of practices
The main judgement criteria are:
- Main:
- Percentage of fetal loss in each group
- Secondary:
- Percentage of invasive tests in each group (amniocentesis or chorionic villus sampling )
- Diagnostic performance of NIPT , in particular false positive and negative
- Percentage of results within 3 weeks and average time interval for results of NIPT
- Percentage of inconclusive results of DPANI
- Percentage of other anomalies discovered at invasive sampling
- Percentage of invasive samples taken despite normal NIPT (either because of later ultrasound anomaly or for maternal reinsurance)
- Association between maternal characteristics ( weight, height, parity , previous history , serum markers ... ) and the results of NIPT
- Cost analysis of NIPT in routine clinical practice
The study will include 2450 high risk women in order to be powered enough to detect a 1% reduction of miscarriages in the group undergoing NIPT instead of routine invasive prenatal diagnosis.
- Conditions
- Down Syndrome
- Being tested
- Non Invasive Prenatal Testing, Invasive Prenatal Testing
- Keywords
- Down, trisomy 21, NIPT, Amniocentesis, miscarriage, invasive, prenatal, screening.
- Medical subject headings
- Down Syndrome, Abortion, Spontaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non Invasive Prenatal TestingProcedure or surgery
Invasive Prenatal TestingProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Non Invasive Prenatal Testing | Experimental | Blood sample Receives: Procedure: Non Invasive Prenatal Testing |
| Invasive Prenatal Testing | Active comparator | CVS or amniocentesis Receives: Procedure: Invasive Prenatal Testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number or miscarriages
Measured: at birth
Secondary outcomes (4)
Number or invasive tests
Measured: at birth
false positive and negative rates of NIPT
Measured: At birth
Dedicated questionnaire for patients
Measured: day 5
Cost of invasive tests and NIPT in euros
measure in euros
Measured: at birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2014 (estimated)
- Study start8 Apr 2014
- Primary completion7 Nov 2016
- Study completion7 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,111 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Laurent J Salomon, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de ParisMichel VEKEMANS, MD, PhD, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02127515
- Sponsor's protocol ID
- P130601
- Other IDs
- 2013-A00998-37
- Acronym
- SAFE 21
- Status last verified
- Sep 2025
- First submitted
- 2 Apr 2014
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Le Bras A, Salomon LJ, Bussieres L, Malan V, Elie C, Mahallati H, Ville Y, Vekemans M, Durand-Zaleski I. Cost-effectiveness of five prenatal screening strategies for trisomies and other unbalanced chromosomal abnormalities: model-based analysis. Ultrasound Obstet Gynecol. 2019 Nov;54(5):596-603. doi: 10.1002/uog.20301.
PubMed 31006923Seror V, L'Haridon O, Bussieres L, Malan V, Fries N, Vekemans M, Salomon LJ, Ville Y; SAFE 21 Study Group. Women's Attitudes Toward Invasive and Noninvasive Testing When Facing a High Risk of Fetal Down Syndrome. JAMA Netw Open. 2019 Mar 1;2(3):e191062. doi: 10.1001/jamanetworkopen.2019.1062.
PubMed 30924894Malan V, Bussieres L, Winer N, Jais JP, Baptiste A, Le Lorc'h M, Elie C, O'Gorman N, Fries N, Houfflin-Debarge V, Sentilhes L, Vekemans M, Ville Y, Salomon LJ; SAFE 21 Study Group. Effect of Cell-Free DNA Screening vs Direct Invasive Diagnosis on Miscarriage Rates in Women With Pregnancies at High Risk of Trisomy 21: A Randomized Clinical Trial. JAMA. 2018 Aug 14;320(6):557-565. doi: 10.1001/jama.2018.9396.
PubMed 30120476
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non Invasive Prenatal Testing of Down Syndrome From Maternal Blood Sample
- ClinicalTrials.gov ID
- NCT02127515
- Acronym / sponsor ID
- SAFE 21 / P130601
- Conditions
- Down Syndrome
- Keywords
- Down, trisomy 21, NIPT, Amniocentesis, miscarriage, invasive, prenatal, screening.
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,111 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 8 Apr 2014 (actual)
- Primary completion
- 7 Nov 2016 (actual)
- Study completion
- 7 Nov 2016 (actual)
- First posted
- 30 Apr 2014 (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.
This is a randomized controlled trial in women at risk following combined prenatal screening for Down Syndrome. Women will be asked about their preferences between NIPT and routine prenatal diagnosis based on a dedicated questionnaire. Women will then be randomized between NIPT and standard invasive prenatal diagnosis.
Detailed description
This is a randomized controlled trial in women at risk following combined prenatal screening for Down Syndrome. Women will be asked about their preferences between NIPT and routine prenatal diagnosis based on a dedicated questionnaire. Women will then be randomized between NIPT and standard invasive prenatal diagnosis.
The general objectives are :
- Promote the rapid and large implementation of Non Invasive Prenatal Testing (NIPT) for Down syndrome.
- Improve the management of women at risk after combined first trimester screening and reduce the number of invasive procedures and induced miscarriages .
- Evaluate NIPT medically (in reducing the rate of invasive sampling and related complications, diagnostic performance and feasibility and acceptability in routine practice) and based on cost-analysis in comparison with standard invasive prenatal diagnosis currently proposed .
- Clarify the conditions of implementation and dissemination of NIPT in the overall organization of prenatal screening for trisomy 21 (and provide data to later adjust or not the combination of tests and thresholds).
Promote the organization as networks of professionals involved in prenatal screening for trisomy 21 in order to allow the emergence of a national system of collection of outcomes to improve the quality of practices
The main judgement criteria are:
- Main:
- Percentage of fetal loss in each group
- Secondary:
- Percentage of invasive tests in each group (amniocentesis or chorionic villus sampling )
- Diagnostic performance of NIPT , in particular false positive and negative
- Percentage of results within 3 weeks and average time interval for results of NIPT
- Percentage of inconclusive results of DPANI
- Percentage of other anomalies discovered at invasive sampling
- Percentage of invasive samples taken despite normal NIPT (either because of later ultrasound anomaly or for maternal reinsurance)
- Association between maternal characteristics ( weight, height, parity , previous history , serum markers ... ) and the results of NIPT
- Cost analysis of NIPT in routine clinical practice
The study will include 2450 high risk women in order to be powered enough to detect a 1% reduction of miscarriages in the group undergoing NIPT instead of routine invasive prenatal diagnosis.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non Invasive Prenatal Testing | Experimental | Procedure: Non Invasive Prenatal TestingBlood sample |
| Invasive Prenatal Testing | Active comparator | Procedure: Invasive Prenatal TestingCVS or amniocentesis |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- pregnant women over 18
- at risk for Down syndrome> 1/250 based on combined screening using ultrasound together with maternal serum markers and prior to fetal karyotyping
- singleton pregnancy
- pregnancy between 11SA et 18SA
- willing a fetal karyotype
Key exclusion criteria (6 listed)
- risk for Down syndrome< 1/250 or >1/5
- NT> 3 mm, PAPP-A or beta HCG <0.3 MoM or >5 MoM
- multiple pregnancy , vanishing twin
- morphological abnormalities at US
- Kown chromosomal anomaly in parents
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 |
|---|---|---|
| Non Invasive Prenatal Testing | Procedure or surgery | Non Invasive Prenatal Testing |
| Invasive Prenatal Testing | Procedure or surgery | Invasive Prenatal Testing |
Primary outcome
Number or miscarriages
Time frame: at birth
4 secondary outcomes
Number or invasive tests
Time frame: at birth
false positive and negative rates of NIPT
Time frame: At birth
Dedicated questionnaire for patients
Time frame: day 5
Cost of invasive tests and NIPT in euros
Time frame: at birth
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 19 Sep 2025.
- Results publication: PubMed 31006923Le Bras A, Salomon LJ, Bussieres L, Malan V, Elie C, Mahallati H, Ville Y, Vekemans M, Durand-Zaleski I. Cost-effectiveness of five prenatal screening strategies for trisomies and other unbalanced chromosomal abnormalities: model-based analysis. Ultrasound Obstet Gynecol. 2019 Nov;54(5):596-603. doi: 10.1002/uog.20301.
- Results publication: PubMed 30924894Seror V, L'Haridon O, Bussieres L, Malan V, Fries N, Vekemans M, Salomon LJ, Ville Y; SAFE 21 Study Group. Women's Attitudes Toward Invasive and Noninvasive Testing When Facing a High Risk of Fetal Down Syndrome. JAMA Netw Open. 2019 Mar 1;2(3):e191062. doi: 10.1001/jamanetworkopen.2019.1062.
- Results publication: PubMed 30120476Malan V, Bussieres L, Winer N, Jais JP, Baptiste A, Le Lorc'h M, Elie C, O'Gorman N, Fries N, Houfflin-Debarge V, Sentilhes L, Vekemans M, Ville Y, Salomon LJ; SAFE 21 Study Group. Effect of Cell-Free DNA Screening vs Direct Invasive Diagnosis on Miscarriage Rates in Women With Pregnancies at High Risk of Trisomy 21: A Randomized Clinical Trial. JAMA. 2018 Aug 14;320(6):557-565. doi: 10.1001/jama.2018.9396.
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Down Syndrome
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.
Laurent J Salomon, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
Michel VEKEMANS, MD, PhD study director
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Non Invasive Prenatal Testing and Invasive Prenatal Testing in people with Down Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 5 inclusion and 6 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 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 or miscarriages (time frame: at birth). 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 NCT02127515, which also lists 3 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 19 Sep 2025.