Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing (ANAMETAB-PRO)
Primary Purpose
Non-Immune Hydrops Fetalis
Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
NON-IMMUNE HYDROPS FETALIS diagnosis
Sponsored by
About this trial
This is an interventional diagnostic trial for Non-Immune Hydrops Fetalis focused on measuring Non-immune hydrops fetalis, Multicentric prospective study, Next Generation Sequencing, Panel
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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
Exclusion Criteria:
- 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
Sites / Locations
- CHU BesançonRecruiting
- CHU PellegrinRecruiting
- Hôpital Femme Mère EnfantRecruiting
- Hôpital d'EstaingRecruiting
- Hôpital Le BocageRecruiting
- CHU GrenobleRecruiting
- CHU LimogesRecruiting
- Hopital Croix RousseRecruiting
- Hopital Nord
- CHU Marseille Timone
- CHU MontpellierRecruiting
- Hôpital Archet 2
- APHP TrousseauRecruiting
- Hopital Lyon SudRecruiting
- CHU Saint EtienneRecruiting
- Hôpital Paule de Viguier;Recruiting
- CHU de Nancy Brabois,Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
pregnant patient whose fetuses have an antenatal NIH
Arm Description
All pregnant patients whose fetuses have an antenatal revelation of NIH from the first trimester ultrasound scan will be included in this study.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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
number of week of amenorrhea of gestation
number of week of amenorrhea of gestation will be measured
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
Full Information
NCT ID
NCT04308603
First Posted
February 28, 2020
Last Updated
January 17, 2022
Sponsor
Hospices Civils de Lyon
1. Study Identification
Unique Protocol Identification Number
NCT04308603
Brief Title
Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
Acronym
ANAMETAB-PRO
Official Title
Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops Fetalis by Massively Parallel Sequencing
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 12, 2021 (Actual)
Primary Completion Date
October 12, 2023 (Anticipated)
Study Completion Date
October 12, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Immune Hydrops Fetalis
Keywords
Non-immune hydrops fetalis, Multicentric prospective study, Next Generation Sequencing, Panel
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
pregnant patient whose fetuses have an antenatal NIH
Arm Type
Experimental
Arm Description
All pregnant patients whose fetuses have an antenatal revelation of NIH from the first trimester ultrasound scan will be included in this study.
Intervention Type
Diagnostic Test
Intervention Name(s)
NON-IMMUNE HYDROPS FETALIS diagnosis
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops by Next Generation Sequencing (NGS) analysis
Description
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.
Time Frame
during pregnancy after the 14th week of amenorrhea
Secondary Outcome Measure Information:
Title
Comparison of percentage of etiology detected between the NGS technique and the biochemical technique.
Description
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.
Time Frame
during pregnancy after the 14th week of amenorrhea
Title
time to return the results in days of NGS techniques
Description
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.
Time Frame
during pregnancy after the 14th week of amenorrhea
Title
number of technical failure of these new tools of NGS techniques
Description
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.
Time Frame
during pregnancy after the 14th week of amenorrhea
Title
Number of cases where the interpretation of the genetic variants did not lead to a conclusion
Description
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
Time Frame
during pregnancy after the 14th week of amenorrhea
Title
number of week of amenorrhea of gestation
Description
number of week of amenorrhea of gestation will be measured
Time Frame
immediately after the child birth
Title
issue of the pregnancy
Description
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
Time Frame
immediately after the child birth
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
MASSARDIER Jerome, MD, PhD
Phone
04 27 85 51 81
Ext
+33
Email
jerome.massardier@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Berthiller Julien
Phone
04 27 85 63 01
Ext
+33
Email
julien.berthiller@chu-lyon.fr
Facility Information:
Facility Name
CHU Besançon
City
Besançon
ZIP/Postal Code
25000 Besancon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MOTTET Nicolas, MD,PhD
Phone
03 81 66 81 66
Ext
+33
Email
ncmottet@gmail.com
First Name & Middle Initial & Last Name & Degree
MOTTET Nicolas, MD,PhD
Facility Name
CHU Pellegrin
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BOUCHGHOUL Hanane, MD,PhD
Phone
05 57 82 25 88
Ext
+33
Email
hanane.bouchghoul@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
BOUCHGHOUL Hanane, MD,PhD
Facility Name
Hôpital Femme Mère Enfant
City
Bron
ZIP/Postal Code
69500
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MASSARDIER Jérôme, MD, PhD
Phone
04 27 85 51 81
Ext
+33
Email
jerome.massardier@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
PERRETON Nathalie
Phone
0427856304
Ext
+33
Email
nathalie.perreton@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
MASSARDIER Jérôme, MD, PhD
Facility Name
Hôpital d'Estaing
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
GALLOT Denis, PU,PH
Phone
04 73 75 07 50
Ext
+33
Email
dgallot@chu-clermontferrand.fr
First Name & Middle Initial & Last Name & Degree
GALLOT Denis, PU,PH
Facility Name
Hôpital Le Bocage
City
Dijon
ZIP/Postal Code
21079
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ROUSSEAU Thierry, MD,PhD
Phone
03 80 29 32 22
Ext
+33
Email
hierry.rousseau@chu-dijon.fr
First Name & Middle Initial & Last Name & Degree
ROUSSEAU Thierry, MD,PhD
Facility Name
CHU Grenoble
City
La Tronche
ZIP/Postal Code
38700
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Devillard Françoise, MD,PhD
Phone
04 76 76 72 85
Ext
+33
Email
FDevillard@chu-grenoble.fr
First Name & Middle Initial & Last Name & Degree
Devillard Françoise, MD,PhD
Facility Name
CHU Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
COSTE-MAZAUD Perrine, MD,PhD
Phone
05 55 05 66 66
Ext
+33
Email
PERRINE.COSTEMAZEAU@chu-limoges.fr
First Name & Middle Initial & Last Name & Degree
COSTE-MAZAUD Perrine, MD,PhD
Facility Name
Hopital Croix Rousse
City
Lyon
ZIP/Postal Code
69004
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
FICHEZ Axel, MD, PhD
Phone
04 72 00 15 58
Ext
+33
Email
Axel.fichez@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
FICHEZ Axel, MD, PhD
Facility Name
Hopital Nord
City
Marseille
ZIP/Postal Code
13000
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
CHAU Cécile, MD,PhD
Phone
04 91 96 80 00
Ext
+33
Email
cecile.chau@ap-hm.fr
First Name & Middle Initial & Last Name & Degree
CHAU Cécile, MD,PhD
Facility Name
CHU Marseille Timone
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SIGAUDY Sabine, MD,PhD
Phone
04 91 96 46 58
Ext
+33
Email
Sabine.SIGAUDY@ap-hm.fr
First Name & Middle Initial & Last Name & Degree
SIGAUDY Sabine, MD,PhD
Facility Name
CHU Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
FUCHS Florent, PU,PH
Phone
04.67.33.65.32
Ext
+33
Email
f-fuchs@chu-montpellier.fr
First Name & Middle Initial & Last Name & Degree
FUCHS Florent, PU,PH
Facility Name
Hôpital Archet 2
City
Nice
ZIP/Postal Code
06200
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ROUZIER Cécile, MD,PhD
Phone
04 92 03 62 43
Ext
+33
Email
rouzier.c@chu-nice.fr
First Name & Middle Initial & Last Name & Degree
ROUZIER Cécile, MD,PhD
Facility Name
APHP Trousseau
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
JOUANNIC Jean-Marie, PU,PH
Phone
01 44 73 52 28
Ext
+33
Email
jean-marie.jouannic@aphp.fr
First Name & Middle Initial & Last Name & Degree
JOUANNIC Jean-Marie, PU,PH
Facility Name
Hopital Lyon Sud
City
Pierre-Bénite
ZIP/Postal Code
69310
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
THONNON Cyrielle, MD, PhD
Phone
04 78 86 56 66
Ext
+33
Email
cyrielle.thonnon@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
THONNON Cyrielle, MD, PhD
Facility Name
CHU Saint Etienne
City
Saint-Priest-en-Jarez
ZIP/Postal Code
42270
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
PRIEUR Fabienne, MD,PhD
Phone
04 77 82 81 16
Ext
+33
Email
Fabienne.Prieur@chu-st-etienne.fr
First Name & Middle Initial & Last Name & Degree
PRIEUR Fabienne, MD,PhD
Facility Name
Hôpital Paule de Viguier;
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
DUBUCS Charlotte, MD,PhD
Phone
05 31 15 61 93
Ext
+33
Email
dubucs.c@chutoulouse.fr
First Name & Middle Initial & Last Name & Degree
DUBUCS Charlotte, MD,PhD
Facility Name
CHU de Nancy Brabois,
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54511
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
PERDRIOLLE Estelle, MD,PhD
Phone
03 83 34 43 29
Ext
+33
Email
e.perdriolle@gmail.com
First Name & Middle Initial & Last Name & Degree
PERDRIOLLE Estelle, MD,PhD
12. IPD Sharing Statement
Learn more about this trial
Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
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