Condition category
Genetic Diseases
Date applied
26/07/2016
Date assigned
03/08/2016
Last edited
28/07/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Down's syndrome, also called also called trisomy 21, is a genetic condition that causes learning disability and characteristic physical features. Screening during pregnancy can determine the likelihood of a baby being born with Down's syndrome. The gold standard screening test is called the combined test because it combines an ultrasound scan with a blood test. The mother’s age and the information from these two tests is used to work out the risk of the baby having Down's syndrome. However, recent research suggests that the test can be improved by adding another test called cell-free fetal DNA screening. Cell-free fetal DNA is DNA from the baby that is found circulating freely in the mother’s blood stream. This additional test could improve screening by reducing the false-positive rate (the number of babies incorrectly diagnosed as having Down’s syndrome). The aim of this study is to compare the false-positive rates of combined screening and cell-free DNA screening for Down's syndrome.

Who can participate?
Women with single pregnancies coming for Down's syndrome screening at 11-13 weeks of pregnancy

What does this study involve?
Participants undergo an ultrasound scan at 11-13 weeks of pregnancy. If fetal defects are found screening is not appropriate and invasive testing is performed. If no anomalies are found then participants are randomly allocated to undergo either cell-free DNA screening or combined screening. Both tests involve blood samples being taken. If there is a positive result invasive testing is offered. The numbers of false-positive cases in the two groups are compared.

What are the possible benefits and risks of participating?
There are no risks as all the tests are already considered to be standard procedures

Where is the study run from?
University of Tuebingen (Germany)

When is the study starting and how long is it expected to run for?
July 2016 to October 2017

Who is funding the study?
Cenata GmbH (Germany)

Who is the main contact?
Prof. Karl Oliver Kagan

Trial website

Contact information

Type

Scientific

Primary contact

Prof Karl Oliver Kagan

ORCID ID

Contact details

University of Tuebingen
Department of Obstetrics and Gynaecology
Calwerstrasse 7
Tuebingen
72076
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2015 - 1

Study information

Scientific title

Comparison of false positive rates in prenatal combined screening and cell free DNA screening for trisomy 21

Acronym

ReFaPo study

Study hypothesis

After a detailed ultrasound examination at 11 - 13 weeks with a normal result, cell-free DNA can reduce the false positive rate compared to combined screening based on maternal age, fetal nuchal translucency, PAPP-A and free beta-hCG.

Ethics approval

University of Tuebingen medical faculty ethics committee, 06/10/2015, ref: 572/2015BO1

Study design

Single-center randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Prenatal screening for trisomy 21

Intervention

Following the normal ultrasound examination, randomization is performed into cell-free DNA screening or combined screening (maternal age, fetal NT, PAPP-A and free beta hCG).

In the cell free DNA (cfDNA) screening group, the risk for trisomy 21 will be calculated based on cell free DNA. For this analysis, blood will be taken and sent to CENATA GmbH who does the analysis. In general the analysis takes 3-5 days. The result will be a risk score. The case is considered to be screen positive if the risk is 1:100 or higher.

In the combined screening group, blood is taken for the analysis of PAPP-A and free beta hCG. The analysis will also done by a commercially driven laboratory. The risk will be calculated by the software of the Fetal Medicine Foundation UK. A risk for trisomy 21 of 1:100 or more is considered to be screen positive. In case of a screen positive result, invasive testing is offered. If the patient opts against invasive testing, we wait until the end of the pregnancy. Screen positive euploid cases are considered to be false positive cases.

All methods (screening by cfDNA, combined screening and invasive testing) are standard procedures in fetal medicine.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Number and proportion of false positive cases in each arm. False positive cases are defined as euploid cases with a risk for trisomy 21 > 1:100. The karyotype will either be obtained by invasive testing somedays after the screening test or after birth.

Secondary outcome measures

1. Number of cases that cannot be randomized (due to fetal defects, increased NT, multiple gestations). This data will become available at 11-13 weeks’ gestation.
2. Time interval between randomization and return of the blood results
3. Number of cases without results in each study arm. This data will be become available latest 2 weeks after the blood sample is taken.
4. Number of women who opt for invasive testing. This data will generally be available within the consecutive 4 weeks after the screening test but theoretically the invasive test can be carried out through the pregnancy.
5. Acceptance of each screening test. The patient will be contacted by us to assess the acceptance level of each of the screening tests. This will be done 4 weeks after the screening test and after birth.

Overall trial start date

01/07/2016

Overall trial end date

01/10/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients coming for prenatal screening for trisomy at 11-13 weeks’ gestation
2. Singleton pregnancies
3. Normal ultrasound examination without increased nuchal translucency thickness >3.5mm and without fetal defects. If NT is increased or there are fetal defects, screening is not appropriate and invasive testing is performed
4. Informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

1400

Participant exclusion criteria

1. Increased nuchal translucency thickness
2. Fetal defects
3. Multiple gestations

Recruitment start date

01/08/2016

Recruitment end date

01/03/2017

Locations

Countries of recruitment

Germany

Trial participating centre

University of Tuebingen
Department of Obstetrics and Gynaecology
72076
Germany

Sponsor information

Organisation

University of Tuebingen (Germany)

Sponsor details

Department of Obstetrics and Gynaecology
Calwerstrasse 7
Tuebingen
72076
Germany

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Cenata GmbH (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We aim to publish the data (results, methodology etc) after the birth of the last enrolled pregnancy. The results will be published in a scientific journal. The data will also be presented at scientific meetings following publication. The data can be made available on an individual basis but an additional statement of the local ethical committee is required for this purpose.

Intention to publish date

01/10/2018

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes