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Trial record 3 of 12 for:    REVELATION

Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing (ANAMETAB-PRO)

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ClinicalTrials.gov Identifier: NCT04308603
Recruitment Status : Not yet recruiting
First Posted : March 16, 2020
Last Update Posted : March 16, 2020
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

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.


Condition or disease Intervention/treatment Phase
Non-Immune Hydrops Fetalis Diagnostic Test: NON-IMMUNE HYDROPS FETALIS diagnosis Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops Fetalis by Massively Parallel Sequencing
Estimated Study Start Date : May 1, 2020
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : November 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Experimental: pregnant patient whose fetuses have an antenatal NIH
All pregnant patients whose fetuses have an antenatal revelation of NIH from the first trimester ultrasound scan will be included in this study.
Diagnostic Test: NON-IMMUNE HYDROPS FETALIS diagnosis
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 Measures :
  1. 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.


Secondary Outcome Measures :
  1. Comparison of percentage of etiology detected between the NGS technique and the biochemical technique. [ Time Frame: during pregnancy after the 14th week of amenorrhea ]
    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.

  2. time to return the results in days of NGS techniques [ Time Frame: during pregnancy after the 14th week of amenorrhea ]
    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.

  3. number of technical failure of these new tools of NGS techniques [ Time Frame: during pregnancy after the 14th week of amenorrhea ]
    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.

  4. 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 ]
    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

  5. number of week of amenorrhea of gestation [ Time Frame: immediately after the child birth ]
    number of week of amenorrhea of gestation will be measured

  6. issue of the pregnancy [ Time Frame: immediately after the child birth ]
    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



Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04308603


Contacts
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Contact: MASSARDIER Jerome, MD, PhD 04 27 85 51 81 ext +33 jerome.massardier@chu-lyon.fr
Contact: Berthiller Julien 04 27 85 63 01 ext +33 julien.berthiller@chu-lyon.fr

Locations
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France
Hôpital Femme Mère Enfant
Bron, France, 69500
Contact: MASSARDIER Jérôme, MD, PhD    04 27 85 51 81 ext +33    jerome.massardier@chu-lyon.fr   
Contact: Berthille Julien    04 27 85 63 01 ext +33    julien.berthiller@chu-lyon.fr   
Principal Investigator: MASSARDIER Jérôme, MD, PhD         
Sponsors and Collaborators
Hospices Civils de Lyon
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT04308603    
Other Study ID Numbers: 69HCL19_0501
2019-A02338-49 ( Other Identifier: ID-RCB )
First Posted: March 16, 2020    Key Record Dates
Last Update Posted: March 16, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
Non-immune hydrops fetalis
Multicentric prospective study
Next Generation Sequencing
Panel
Additional relevant MeSH terms:
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Hydrops Fetalis
Metabolism, Inborn Errors
Edema
Genetic Diseases, Inborn
Metabolic Diseases
Erythroblastosis, Fetal
Fetal Diseases
Pregnancy Complications
Hematologic Diseases
alpha-Thalassemia
Thalassemia
Hemoglobinopathies
Immune System Diseases