Non Invasive Prenatal Testing of Down Syndrome (SAFE 21)

• ClinicalTrials.gov Identifier: NCT02127515
• Recruitment Status: Completed
• Last Update Posted: March 26, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Down Syndrome	Procedure: Non Invasive Prenatal Testing; Procedure: Invasive Prenatal Testing	Not Applicable

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2111 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Non Invasive Prenatal Testing of Down Syndrome From Maternal Blood Sample
• Actual Study Start Date: April 8, 2014
• Actual Primary Completion Date: November 7, 2016
• Actual Study Completion Date: November 7, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Non Invasive Prenatal Testing; Blood sample	Procedure: Non Invasive Prenatal Testing
Active Comparator: Invasive Prenatal Testing; CVS or amniocentesis	Procedure: Invasive Prenatal Testing

Outcome Measures

Primary Outcome Measures :

1. Number or miscarriages [ Time Frame: at birth ]

Secondary Outcome Measures :

1. Number or invasive tests [ Time Frame: at birth ]
2. false positive and negative rates of NIPT [ Time Frame: At birth ]
3. Dedicated questionnaire for patients [ Time Frame: day 5 ]
4. Cost of invasive tests and NIPT in euros [ Time Frame: at birth ]
   measure in euros

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Locations

France

Hôpital Necker- Enfants Malades

Paris, France, 75015

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

• Principal Investigator: Laurent J Salomon, MD, PhD; Assistance Publique - Hôpitaux de Paris
• Study Director: Michel VEKEMANS, MD, PhD; Assistance Publique - Hôpitaux de Paris

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Malan 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.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02127515
• Other Study ID Numbers: P130601; 2013-A00998-37 ( Other Identifier: ANSM )
• First Posted: April 30, 2014
• Last Update Posted: March 26, 2021
• Last Verified: March 2021

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Down, trisomy 21; NIPT; Amniocentesis; miscarriage; invasive; prenatal; screening.

Additional relevant MeSH terms:

Down Syndrome; Syndrome; Disease; Pathologic Processes; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn