AneuploidyNCT04077060
First Trimester Risk Assessment Based on Ultrasound and Cell-free DNA vs Combined Screening
A study testing NIPT and combined screening in people with Aneuploidy, run by Federico II University at 1 site in Italy.
Trial summary
There is an ongoing debate regarding how cell-free DNA (cfDNA) screening can best be incorporated into current prenatal screening algorithms for chromosomal abnormalities. Test performance of cfDNA has been shown to be better that first-trimester combined screening (FTCS). Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Aneuploidy
- What is being tested?
- NIPT and combined screening
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 26 Aug 2019to 15 Feb 2020
- 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 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Pregnant women with singleton gestations
- ≤12 6/7 weeks of gestation
- Normal ultrasound examination at the time of randomization
- >18 <45 years
- Crown-rump length (CRL) <84 mm at the time of randomization
Who cannot join
- Multiple gestations, including vanishing twins
- >12 6/7 weeks of gestation
- Ectopic pregnancy
- Abnormal ultrasound examination at the time of first prenatal visit
- Women who are unconscious, severly ill, mentally handicapped, or under the age of 18 years.
- Women who have already planned for invasive prenatal testing, e.g. for a history of prior child or pregnancy with chromosomal or genetic abnormalities
- CRL >84mm at the time of randomization
Trial locations and contacts
1 site in 1 country.
About this study
Official title: First Trimester Risk Assessment Based on Ultrasound and Cell-free DNA vs Combined Screening: Women's Experience
There is an ongoing debate regarding how cell-free DNA (cfDNA) screening can best be incorporated into current prenatal screening algorithms for chromosomal abnormalities.
Test performance of cfDNA has been shown to be better that first-trimester combined screening (FTCS). However, the cost of the cfDNA testing is considered too high to adopt as first line screening. Moreover, FTCS includes a detailed ultrasound examination of the fetus with nuchal translucency (NT) measurement that allows for early detection of fetal abnormalities.
Read more
An approach in which every woman are offered an early anatomy scan along with cfDNA may also be a reasonable option. Recently a randomized controlled trial, including 1,518 women with singleton pregnancy undergoing first-trimester screening, compared the screening performance of FTCS with an approach that uses the combination of a detailed ultrasound examination and cfDNA analysis. The trial showed that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination along cfDNA was associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy.
Despite robust evidence on the very high detection rate of cfDNA in detecting trisomy 21, literature is lacking on data regarding women's experience and emotional well-being and satisfaction after test-results of women offered cfDNA compared to those offered FTCS.
- Conditions
- Aneuploidy
- Being tested
- NIPT, combined screening
- Medical subject headings
- Aneuploidy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIPTDiagnostic test
Women randomized in the intervention group will be offered cfDNA screening, along with an early detailed anatomy scan, including nuchal measurement, at 11-13 weeks of gestation. cfDNA analysis will include a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. NIPT will be performed at the time of randomization or after if gestational age at randomization < 9 6/7 weeks of gestation.
Women in both groups will be given oral counseling by obstetricians and will be counseled about test procedures, reporting time, test sensitivity and specificity, and the necessity to confirm abnormal screening results with invasive testing.
combined screeningDiagnostic test
Control group includes the standard of care. In our department, first-trimester risk assessment is performed routinely at 11-13 weeks of gestation by FTCS as per standard of care. FTCS includes crown-rump length, NT measurements, and a detailed ultrasound examination based on ISUOG guidelines. All operators who perform this examination are certified by the UK Fetal Medicine Foundation (FMF). A specific risk for aneuploidy is not calculated if NT measurement is >3.5 mm or if fetal anomaly is identified. These cases are deemed to be at a very high risk for chromosomal abnormalities and are offered invasive testing.
| Study group | Role | What they receive |
|---|---|---|
| NIPT | Experimental | Women randomized in the intervention group will be offered cfDNA screening, along with an early detailed anatomy scan, including nuchal measurement, at 11-13 weeks of gestation. cfDNA analysis will include a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. NIPT will be performed at the time of randomization or after if gestational age at randomization < 9 6/7 weeks of gestation. Receives: Diagnostic Test: NIPT |
| Combined screening | Other | Control group includes the standard of care. In our department, first-trimester risk assessment is performed routinely at 11-13 weeks of gestation by FTCS as per standard of care. FTCS includes crown-rump length, NT measurements, and a detailed ultrasound examination based on ISUOG guidelines. All operators who perform this examination are certified by the UK Fetal Medicine Foundation (FMF). A specific risk for aneuploidy is not calculated if NT measurement is >3.5 mm or if fetal anomaly is identified. These cases are deemed to be at a very high risk for chromosomal abnormalities and are offered invasive testing. Receives: Diagnostic Test: combined screening |
What is being measured
The primary outcome is the main question the study is designed to answer.
reassurance
women will be asked about three questions, with up to 35 point for each question. 1) are you reassured about the test? 2) are you sure the test is correct? 3) test give me certain reassurance about the syndrome of my child
Measured: at the time of screening test
Anxiety
anxiety test assessed by State-Trait Anxiety Inventory (STAI)
Measured: at the time of screening test
Satisfaction of the pregnant women
women will be asked if retrospectively they are happy with the assigned screening test as post-test satisfaction questionnaire:
- Not all applicable (5 points)
- Hardly applicable (10 points)
- Somewhat applicable (20 points)
- Very much applicable (35 points)
Measured: 11-13 weeks of gestation
False positive rate
False positive rate for any trosomy and for trisomy 21
Measured: 1 week after test
Anxiety
anxiety test assessed by The Pregnancy-Related Anxiety Questionnaire (PRAQ-R)
Measured: at the time of screening test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2019
- Study start26 Aug 2019
- Primary completion15 Jan 2020
- Study completion15 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AneuploidyStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gabriele Saccone, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04077060
- Sponsor's protocol ID
- 209/19
- Status last verified
- Feb 2020
- First submitted
- 26 Aug 2019
- Last updated
- 24 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Migliorini S, Saccone G, Silvestro F, Massaro G, Arduino B, D'Alessandro P, Petti MT, Paino JAC, Guida M, Locci M, Zullo F. First-trimester screening based on cell-free DNA vs combined screening: A randomized clinical trial on women's experience. Prenat Diagn. 2020 Oct;40(11):1482-1488. doi: 10.1002/pd.5800. Epub 2020 Aug 13.
PubMed 32683755
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First Trimester Risk Assessment Based on Ultrasound and Cell-free DNA vs Combined Screening: Women's Experience
- ClinicalTrials.gov ID
- NCT04077060
- Acronym / sponsor ID
- 209/19
- Conditions
- Aneuploidy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- 26 Aug 2019 (actual)
- Primary completion
- 15 Jan 2020 (actual)
- Study completion
- 15 Feb 2020 (actual)
- First posted
- 4 Sep 2019 (actual)
- 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.
There is an ongoing debate regarding how cell-free DNA (cfDNA) screening can best be incorporated into current prenatal screening algorithms for chromosomal abnormalities.
Test performance of cfDNA has been shown to be better that first-trimester combined screening (FTCS). However, the cost of the cfDNA testing is considered too high to adopt as first line screening. Moreover, FTCS includes a detailed ultrasound examination of the fetus with nuchal translucency (NT) measurement that allows for early detection of fetal abnormalities.
An approach in which every woman are offered an early anatomy scan along with cfDNA may also be a reasonable option. Recently a randomized controlled trial, including 1,518 women with singleton pregnancy undergoing first-trimester screening, compared the screening performance of FTCS with an approach that uses the combination of a detailed ultrasound examination and cfDNA analysis. The trial showed that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination along cfDNA was associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy.
Despite robust evidence on the very high detection rate of cfDNA in detecting trisomy 21, literature is lacking on data regarding women's experience and emotional well-being and satisfaction after test-results of women offered cfDNA compared to those offered FTCS.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NIPT | Experimental | Diagnostic Test: NIPTWomen randomized in the intervention group will be offered cfDNA screening, along with an early detailed anatomy scan, including nuchal measurement, at 11-13 weeks of gestation. cfDNA analysis will include a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. NIPT will be performed at the time of randomization or after if gestational age at randomization < 9 6/7 weeks of gestation. |
| Combined screening | Other | Diagnostic Test: combined screeningControl group includes the standard of care. In our department, first-trimester risk assessment is performed routinely at 11-13 weeks of gestation by FTCS as per standard of care. FTCS includes crown-rump length, NT measurements, and a detailed ultrasound examination based on ISUOG guidelines. All operators who perform this examination are certified by the UK Fetal Medicine Foundation (FMF). A specific risk for aneuploidy is not calculated if NT measurement is >3.5 mm or if fetal anomaly is identified. These cases are deemed to be at a very high risk for chromosomal abnormalities and are offered invasive testing. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Pregnant women with singleton gestations
- ≤12 6/7 weeks of gestation
- Normal ultrasound examination at the time of randomization
- >18 <45 years
- Crown-rump length (CRL) <84 mm at the time of randomization
Key exclusion criteria (7 listed)
- Multiple gestations, including vanishing twins
- >12 6/7 weeks of gestation
- Ectopic pregnancy
- Abnormal ultrasound examination at the time of first prenatal visit
- Women who are unconscious, severly ill, mentally handicapped, or under the age of 18 years.
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 |
|---|---|---|
| NIPTWomen randomized in the intervention group will be offered cfDNA screening, along with an early detailed anatomy scan, including nuchal measurement, at 11-13 weeks of gestation. cfDNA analysis will include a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. NIPT will be performed at the time of randomization or after if gestational age at randomization < 9 6/7 weeks of gestation. Women in both groups will be given oral counseling by obstetricians and will be counseled about test procedures, reporting time, test sensitivity and specificity, and the necessity to confirm abnormal screening results with invasive testing. | Diagnostic test | NIPT |
| combined screeningControl group includes the standard of care. In our department, first-trimester risk assessment is performed routinely at 11-13 weeks of gestation by FTCS as per standard of care. FTCS includes crown-rump length, NT measurements, and a detailed ultrasound examination based on ISUOG guidelines. All operators who perform this examination are certified by the UK Fetal Medicine Foundation (FMF). A specific risk for aneuploidy is not calculated if NT measurement is >3.5 mm or if fetal anomaly is identified. These cases are deemed to be at a very high risk for chromosomal abnormalities and are offered invasive testing. | Diagnostic test | Combined screening |
Primary outcome
reassurance
Time frame: at the time of screening test
women will be asked about three questions, with up to 35 point for each question. 1) are you reassured about the test? 2) are you sure the test is correct? 3) test give me certain reassurance about the syndrome of my child
Anxiety
Time frame: at the time of screening test
anxiety test assessed by State-Trait Anxiety Inventory (STAI)
Satisfaction of the pregnant women
Time frame: 11-13 weeks of gestation
women will be asked if retrospectively they are happy with the assigned screening test as post-test satisfaction questionnaire: * Not all applicable (5 points) * Hardly applicable (10 points) * Somewhat applicable (20 points) * Very much applicable (35 points)
False positive rate
Time frame: 1 week after test
False positive rate for any trosomy and for trisomy 21
Anxiety
Time frame: at the time of screening test
anxiety test assessed by The Pregnancy-Related Anxiety Questionnaire (PRAQ-R)
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 24 Feb 2020.
- Derived from this study: PubMed 32683755Migliorini S, Saccone G, Silvestro F, Massaro G, Arduino B, D'Alessandro P, Petti MT, Paino JAC, Guida M, Locci M, Zullo F. First-trimester screening based on cell-free DNA vs combined screening: A randomized clinical trial on women's experience. Prenat Diagn. 2020 Oct;40(11):1482-1488. doi: 10.1002/pd.5800. Epub 2020 Aug 13.
- Individual participant dataSharing planned: No
Related trials for Aneuploidy
RecruitingObservational study
Pilot Study of Discarded Blastocysts
Infertility (IVF Patients)
RecruitingObservational study
The ADVANCE (Assay Development and Validation for Pre-Natal and Obstetric Conditions) Study is the Largest U.S.-Based Prospective Study Demonstrating a Circulating Fetal Cell (CFC) Based Approach to Non-invasive Fetal Risk Assessment
Pregnant Individuals, Aneuploidy
Not yet recruiting
AI-Assisted Euploid Embryo Selection for Single-Blastocyst Transfer in Women of Advanced Maternal Age
Female Infertility
RecruitingObservational study
Detection of Aneuploidy in Cell Free DNA to Improve the Sensitivity of Diagnostic Peritoneal Lavage in Gastric Cancer
Gastric Cancer
RecruitingObservational study
Specimen Collection From Pregnant Women at Increased Risk for Fetal Aneuploidy
Down Syndrome, Fetal Aneuploidy
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NIPT and combined screening in people with Aneuploidy, run by Federico II University at 1 site in Italy.
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 7 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 24 Feb 2020. 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 Italy. 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?
reassurance (time frame: at the time of screening test). The study lists 5 primary outcomes in all. 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 NCT04077060, which also lists 1 linked publication.
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 24 Feb 2020.