Non-Immune Hydrops FetalisANAMETAB-PRONCT04308603
Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
A study testing NON-IMMUNE HYDROPS FETALIS diagnosis in people with Non-Immune Hydrops Fetalis, run by Hospices Civils de Lyon at 17 sites in France.
Trial summary
A fetal hydrops, also called a fetal anasarca, is the buildup of fluid in the serosa and / or fetal subcutaneous tissue. The diagnosis is made by ultrasound, possibly from the first trimester of pregnancy. The etiologies of hydrops can be immune or non-immune. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Non-Immune Hydrops Fetalis
- What is being tested?
- NON-IMMUNE HYDROPS FETALIS diagnosis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 17 sitesFrance
- Study dates
- 12 Apr 2021to 12 Apr 2024
- 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
- patient> 18 years old
- Single Pregnancy
- Progressive pregnancy greater than 11 weeks: Fetal death in utero in a fetus previously known to be a carrier of non Immun Hydrops (NIH) is not an exclusion criterion.
- Presence of an ultrasound defined as follows and confirmed by a multidisciplinary prenatal diagnostic center CPDPN:
- Before 14 weeks: Generalized subcutaneous edema descending to the abdomen, associated or not with peri-visceral effusion
- After 14 weeks: presence of at least 2 of the following criteria: ascites, pleural effusion, pericardial effusion, subcutaneous edema, placental edema, hydramnios.
Show all 11Show fewer
- Persistent hygroma after 14 weeks of amenorrhea
- Persistent isolated perivisceral effusions without etiologies found
- Patient having an invasive diagnostic sample (amniocentesis)
- Social insured in France
- Patient who signed the informed consent of the study
Who cannot join
- NIH whose diagnosis is known and confirmed as non-metabolic by a CPDPN
- Non-progressive pregnancy with Fetal Death in utero with normal previous ultrasound monitoring
- Refusal of invasive diagnostic sampling
- Patient under legal protection measure
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
France17 sites
CHU Besançon
Besançon, 25000 Besancon
CHU Pellegrin
Bordeaux, 33076
Hôpital Femme Mère Enfant
Bron, 69500
Hôpital d'Estaing
Clermont-Ferrand, 63003
Hôpital Le Bocage
Dijon, 21079
CHU Grenoble
La Tronche, 38700
CHU Limoges
Limoges, 87042
Hopital Croix Rousse
Lyon, 69004
Hopital Nord
Marseille, 13000
CHU Marseille Timone
Marseille, 13005
CHU Montpellier
Montpellier, 34295
Hôpital Archet 2
Nice, 06200
APHP Trousseau
Paris, 75012
Hopital Lyon Sud
Pierre-Bénite, 69310
CHU Saint Etienne
Saint-Priest-en-Jarez, 42270
Hôpital Paule de Viguier;
Toulouse, 31059
CHU de Nancy Brabois,
Vandœuvre-lès-Nancy, 54511
About this study
Official title: Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops Fetalis by Massively Parallel Sequencing
A fetal hydrops, also called a fetal anasarca, is the buildup of fluid in the serosa and / or fetal subcutaneous tissue. The diagnosis is made by ultrasound, possibly from the first trimester of pregnancy.
The etiologies of hydrops can be immune or non-immune. The historically classic immune causes are linked to fetal-maternal alloimmunizations in erythrocyte blood groups. The implementation of systematic prevention of these anti rhesus immunizations since the 1970s has significantly reduced the incidence of immune hydrops Non-immune hydrops (NIH) now represent 90% of fetal hydrops. Known causes of NIH can be classified in several ways depending on the mechanism or organ involved.
Read more
The prognosis for NIH is closely linked to the cause. Fetal anemia due to maternal-fetal infections can heal spontaneously or give rise to in utero transfusions. Cardiac rhythm abnormalities are accessible to medical treatment. Chylothorax compressions may benefit from in utero drainage, but chromosomal or metabolic causes cannot benefit from antenatal care. The term of pregnancy in which the hydrops is discovered also has an impact on survival, which however remains poor.
In France, certain pathologies can be considered as particularly serious without the possibility of treatment and give rise to a request for medical termination of pregnancy. This possibility is subject to acceptance by two practitioners who are members of a multidisciplinary prenatal diagnostic center (CPDPN). This preliminary multidisciplinary reflection participates in the development of prenatal counseling with the greatest precision in diagnostic hypotheses. This prenatal advice is essential for a couple on the decision to make a pregnancy in progress but also for future pregnancies, given the 25% risk of recurrence due to the autosomal recessive mode of transmission.
Thus the current screening strategy for inherited metabolic diseases on amniotic fluid is fragmented. The resulting subdiagnosis explains the objective of the study of using the new high throughput sequencing techniques (NGS) in this indication. This approach should make it possible to reduce the number of cases classified as idiopathic, to allow the parents concerned to receive suitable genetic counseling with a view to new pregnancies, and to refine the knowledge of the prenatal epidemiology of these pathologies.
- Conditions
- Non-Immune Hydrops Fetalis
- Being tested
- NON-IMMUNE HYDROPS FETALIS diagnosis
- Keywords
- Non-immune hydrops fetalis, Multicentric prospective study, Next Generation Sequencing, Panel
- Medical subject headings
- Hydrops Fetalis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NON-IMMUNE HYDROPS FETALIS diagnosisDiagnostic test
Amniotic liquid of each selected patients will be tested by both technic to describe and detect etiological information. Each patient will be tested using the current procedure with a defined panel of genes as well as with the NGS procedure. The results of both procedures will be compared.
| Study group | Role | What they receive |
|---|---|---|
| pregnant patient whose fetuses have an antenatal NIH | Experimental | All pregnant patients whose fetuses have an antenatal revelation of NIH from the first trimester ultrasound scan will be included in this study. Receives: Diagnostic Test: NON-IMMUNE HYDROPS FETALIS diagnosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops by Next Generation Sequencing (NGS) analysis
Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops can be detected by Next Generation Sequencing (NGS) analysis of the gene panel incriminated in inherited metabolic malformation compared to the proportion of fetuses for which a genetic anomaly has been identified by the technique current standard biochemical.
Measured: during pregnancy after the 14th week of amenorrhea
Secondary outcomes (6)
Comparison of percentage of etiology detected between the NGS technique and the biochemical technique.
The percentage of the following etiology of interest (Cardiovascular abnormalities, Chromosomal abnormalities, Haematological abnormalities, infections, Thoracic anomalies, Twin-to-twin transfusion syndromes, Uro-Nephrological Anomalies, Abdominal anomalies, Lymphatic dysplasia, Fetal or placental tumors, osteochondrodysplasias. syndromic, Hereditary Metabolism Diseases) will be assessed and compared between the 2 methods.
Measured: during pregnancy after the 14th week of amenorrhea
time to return the results in days of NGS techniques
The delay of answer will be defined by the time to return the results by analysis of the panel of genes tested compared to the current standard biochemical technique, measured between the date of completion of the prenatal diagnosis procedure and the date of communication of the results to the parents.
Measured: during pregnancy after the 14th week of amenorrhea
number of technical failure of these new tools of NGS techniques
Number of technical failures: unable to extract DNA, too little DNA, failed sequencing), and analysis of these failures will be measured and compared to the current standard biochemical technique.
Measured: during pregnancy after the 14th week of amenorrhea
Number of cases where the interpretation of the genetic variants did not lead to a conclusion
by the number of cases where the interpretation of the genetic variants highlighted did not allow concluding on the imputability for the clinical picture will be assessed of these new tools of NGS techniques
Measured: during pregnancy after the 14th week of amenorrhea
number of week of amenorrhea of gestation
number of week of amenorrhea of gestation will be measured
Measured: immediately after the child birth
issue of the pregnancy
The percentage of death in utero, the percentage of medical termination of pregnancy, the percentage of neonatal survival and the percentage of pregnancy continued until the end will be calculated
Measured: immediately after the child birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start12 Apr 2021
- Primary completion12 Apr 2024
- Study completion12 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Immune Hydrops FetalisStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04308603
- Sponsor's protocol ID
- 69HCL19_0501
- Other IDs
- 2019-A02338-49
- Acronym
- ANAMETAB-PRO
- Status last verified
- Nov 2024
- First submitted
- 28 Feb 2020
- Last updated
- 8 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops Fetalis by Massively Parallel Sequencing
- ClinicalTrials.gov ID
- NCT04308603
- Acronym / sponsor ID
- ANAMETAB-PRO / 69HCL19_0501
- Conditions
- Non-Immune Hydrops Fetalis
- Keywords
- Non-immune hydrops fetalis, Multicentric prospective study, Next Generation Sequencing, Panel
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 12 Apr 2021 (actual)
- Primary completion
- 12 Apr 2024 (actual)
- Study completion
- 12 Apr 2024 (actual)
- First posted
- 16 Mar 2020 (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.
A fetal hydrops, also called a fetal anasarca, is the buildup of fluid in the serosa and / or fetal subcutaneous tissue. The diagnosis is made by ultrasound, possibly from the first trimester of pregnancy.
The etiologies of hydrops can be immune or non-immune. The historically classic immune causes are linked to fetal-maternal alloimmunizations in erythrocyte blood groups. The implementation of systematic prevention of these anti rhesus immunizations since the 1970s has significantly reduced the incidence of immune hydrops Non-immune hydrops (NIH) now represent 90% of fetal hydrops. Known causes of NIH can be classified in several ways depending on the mechanism or organ involved.
The prognosis for NIH is closely linked to the cause. Fetal anemia due to maternal-fetal infections can heal spontaneously or give rise to in utero transfusions. Cardiac rhythm abnormalities are accessible to medical treatment. Chylothorax compressions may benefit from in utero drainage, but chromosomal or metabolic causes cannot benefit from antenatal care. The term of pregnancy in which the hydrops is discovered also has an impact on survival, which however remains poor.
In France, certain pathologies can be considered as particularly serious without the possibility of treatment and give rise to a request for medical termination of pregnancy. This possibility is subject to acceptance by two practitioners who are members of a multidisciplinary prenatal diagnostic center (CPDPN). This preliminary multidisciplinary reflection participates in the development of prenatal counseling with the greatest precision in diagnostic hypotheses. This prenatal advice is essential for a couple on the decision to make a pregnancy in progress but also for future pregnancies, given the 25% risk of recurrence due to the autosomal recessive mode of transmission.
Thus the current screening strategy for inherited metabolic diseases on amniotic fluid is fragmented. The resulting subdiagnosis explains the objective of the study of using the new high throughput sequencing techniques (NGS) in this indication. This approach should make it possible to reduce the number of cases classified as idiopathic, to allow the parents concerned to receive suitable genetic counseling with a view to new pregnancies, and to refine the knowledge of the prenatal epidemiology of these pathologies.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pregnant patient whose fetuses have an antenatal NIH | Experimental | Diagnostic Test: NON-IMMUNE HYDROPS FETALIS diagnosisAll pregnant patients whose fetuses have an antenatal revelation of NIH from the first trimester ultrasound scan will be included in this study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- patient> 18 years old
- Single Pregnancy
- Progressive pregnancy greater than 11 weeks: Fetal death in utero in a fetus previously known to be a carrier of non Immun Hydrops (NIH) is not an exclusion criterion.
- Presence of an ultrasound defined as follows and confirmed by a multidisciplinary prenatal diagnostic center CPDPN:
- Before 14 weeks: Generalized subcutaneous edema descending to the abdomen, associated or not with peri-visceral effusion
Key exclusion criteria (4 listed)
- NIH whose diagnosis is known and confirmed as non-metabolic by a CPDPN
- Non-progressive pregnancy with Fetal Death in utero with normal previous ultrasound monitoring
- Refusal of invasive diagnostic sampling
- Patient under legal protection measure
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-IMMUNE HYDROPS FETALIS diagnosisAmniotic liquid of each selected patients will be tested by both technic to describe and detect etiological information. Each patient will be tested using the current procedure with a defined panel of genes as well as with the NGS procedure. The results of both procedures will be compared. | Diagnostic test | pregnant patient whose fetuses have an antenatal NIH |
Primary outcome
Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops by Next Generation Sequencing (NGS) analysis
Time frame: during pregnancy after the 14th week of amenorrhea
Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops can be detected by Next Generation Sequencing (NGS) analysis of the gene panel incriminated in inherited metabolic malformation compared to the proportion of fetuses for which a genetic anomaly has been identified by the technique current standard biochemical.
6 secondary outcomes
Comparison of percentage of etiology detected between the NGS technique and the biochemical technique.
Time frame: during pregnancy after the 14th week of amenorrhea
time to return the results in days of NGS techniques
Time frame: during pregnancy after the 14th week of amenorrhea
number of technical failure of these new tools of NGS techniques
Time frame: during pregnancy after the 14th week of amenorrhea
Number of cases where the interpretation of the genetic variants did not lead to a conclusion
Time frame: during pregnancy after the 14th week of amenorrhea
number of week of amenorrhea of gestation
Time frame: immediately after the child birth
issue of the pregnancy
Time frame: immediately after the child 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 8 Nov 2024.
- Individual participant dataSharing planned: No
Related trials for Non-Immune Hydrops Fetalis
Enrolling by invitation
Uncovering the Etiologies of Non-immune Hydrops Fetalis
Non-Immune Hydrops Fetalis
RecruitingObservational study
Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
High Risk Pregnancy, Congenital Heart Disease
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.
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NON-IMMUNE HYDROPS FETALIS diagnosis in people with Non-Immune Hydrops Fetalis, run by Hospices Civils de Lyon at 17 sites 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 11 inclusion and 4 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 8 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites 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?
Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops by Next Generation Sequencing (NGS) analysis (time frame: during pregnancy after the 14th week of amenorrhea). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Nov 2024.