Generalized Neonatal Screening of Severe Combined Immunodeficiencies

Severe Combined Immunodeficiency, Atypical Clinical Trial

— DEPISTREC  

Official title:

Evaluation of the Clinical Utility and Cost Effectiveness Ratio of Generalized Neonatal Screening for Severe Combined Immunodeficiencies (SCID) by Quantification of TRECs on Guthrie Cards

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02244450
• Other study ID #: RC14_0030
• Status: Completed
• Phase: N/A
• Start date: December 2014
• Est. completion date: April 28, 2018

Study information

• Verified date: July 2018
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Severe combined Immunodeficiencies ( SCID ) are a group of inherited diseases of the immune system by characterised profound abnormalities of T cell development . Infants with SCID require prompt clinical response to Prevent life -threatening infection and studies show significantly improved survival in babies Diagnosed at birth as a result of previous family history . SCID follows criteria for population -based newborn screening since it is asymptomatic at birth and fatal within the first year of life, the confirmation of the disease is easy, there is a curative treatment , and it is known that early stem cell transplantation improves survival . Quantification of TRECs (T- cell receptor excision circles ) in DNA extracted from Guthrie samples is a sensitive screening test for Specific and SCID .

The investigators propose in this study to perform a neonatal screening of SCID , in a population of 200,000 babies over a period of two years .

The investigators propose to study the clinical utility and cost effectiveness ratio, and SCID screening to demonstrate that could result in a broad benefit to Individuals detected , making screening relatively cost-effective in spite of the low incidence of the disease .

Description:

The project proposes to study the feasibility and cost-effectiveness ratio ( time management and life expectancy to 10 years) of generalized neonatal screening for SCID children by offering this screening to 200 000 children (100 000 children per year) over the entire territory. Prospective control group consists of children diagnosed with SCID out of 700,000 annual births who do not benefit from screening.

The protocol will be leant against the existing newborn screening , that is to say two more drops of blood are placed on a second Guthrie card when current screening (72 hours of life ) is performed after parents' information and consent. Eleven newborn screening regional associations will be involved with the inclusion of children in about 50 maternity hospitals. The card drawn for the protocol will follow the usual network except that the test for quantifying TRECs will be realized in two laboratories instead of eleven laboratories assigned to RA . Investigative Regional Associations (RAs) represent nearly 600,000 births / year and the amount of 200,000 children will be achieved in two years (duration of inclusion) . All children born in the participating maternity may be included if they meet the inclusion criteria. The result of the screening test for SCID will be available within 21 days after birth, provided that there is no need to request a new sample.

At each of eleven RA is associated a pediatrician referent for immune deficiencies, member of the french reference center (CEREDIH) and who will be responsible to call the parents, offer them a consultation and further exploration if the result of screening is assumed positive.

Analysis of cards from 200,000 children will give the following information:

• Number of children with a presumptive positive screening , requiring a call by the referent pediatrician, consultation and exploration of lymphocyte subpopulations

• Number of children with a negative screening

• Number of children with an inconclusive screening (lack of TRECs and lack of amplification of the reference gene) and requiring a new card,

A micro- costing study will be conducted to assess the cost of testing .

This group of 200,000 children is the experimental group to assess the cost of screening , acceptability by parents (participation rate), the recall rate for abnormal or inconclusive result, the rate of follow-up time for results , the incidence of disease . It will also allow to calculate the specificity of the method .

At the end of the inclusions, the vital status at 18 months with cause of death will be sought for the 200 000 children included , with the CESP ( Centre de Recherche en Epidemiologie et Santé des Populations) via RNIPP (Répertoire National d'Identification des Personnes Physiques) and CepiDc ( Centre d'Epidémiologie sur les causes médicales de décès) . This will establish whether there are SCID in this population which were not detected at birth. Furthermore, the investigators include in the study SCID children diagnosed without screening by pediatricians local referents DIP (including Necker main transplant center) . This will enable to approach the sensitivity of the method . All these data allow the calculation of the predictive values of the test.

In this experimental group will be isolated a group of individuals who screened positive and diagnosed as true SCID . Clinical data for these patients will be collected in an electronic CRF ( CRF ) by the pediatrician referral protocol (Dr Thomas C ) , including:

• The dates and results of explorations : lymphocyte subpopulations , blood count, determination of immunoglobulin levels

• The diagnosis made with identification of the genetic defect

• The date of care before curative treatment ( protected area isolation , anti -infective drugs )

• , Bacterial , fungal anti -viral treatments , and other

• The date of transplant, type of transplant or other treatment ... ...

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190539
• Est. completion date: April 28, 2018
• Est. primary completion date: April 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 18 Months

Eligibility

Inclusion Criteria:

• Screening Group: Newborn on day 3 of birth (premature and non premature)

• Control group: Patients diagnosed with SCID without screening at participating centers

Exclusion Criteria:

• Lack of parental consent

• Children whose parents are adults under guardianship,

• Children without health insurance, for the screening group:

• The early exit of the child from the maternity hospital

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Severe Combined Immunodeficiency
• Severe Combined Immunodeficiency, Atypical

Intervention

Biological:
• SCID screening

Locations

Country	Name	City	State
France	Angers Private Hospital Clinique de l'Anjou	Angers
France	Angers University Hospital	Angers
France	Argenteuil Hospital	Argenteuil
France	Aulnay-sous-Bois Hospital CHI Robert Ballanger	Aulnay-sous-Bois
France	Bordeaux Maison de Santé Protestante Bordeaux Bagatelle	Bordeaux
France	Bordeaux Private Hospital Polyclinique Bordeuax Nord Aquitaine	Bordeaux
France	Bordeaux University Hospital	Bordeaux
France	Corbeil Essonnes Hospital Sud Francilien	Corbeil Essonnes
France	Créteil Hospital	Créteil
France	Dijon University Hospital	Dijon
France	Grenoble University Hospital	Grenoble
France	Le Blanc Mesnil Private Hospital	Le Blanc Mesnil
France	Lens Hospital	Lens
France	Libourne Maternity Hospital	Libourne
France	Lille University Hospital	Lille
France	Lormont Maternity Hospital Rive Droite	Lormont
France	Lyon Maternity Hospital	Lyon
France	Lyon University Hospital	Lyon
France	Marseille Saint-Joseph Hospital	Marseille
France	Marseille University Hospital	Marseille
France	Marseille University Hospital La Conception	Marseille
France	Marseille University Hospital Nord	Marseille
France	Meaux Hospital	Meaux
France	Montreuil Hospital CHI André Grégroie	Montreuil
France	Nantes Private Hospital Clinique Jules Verne	Nantes
France	Nantes University Hospital	Nantes
France	Nantes University Hospital	Nantes
France	Paris Hospital Saint-Joseph	Paris
France	Paris Necker University Hospital	Paris
France	Paris University Hospital Armand-Trousseau	Paris
France	Paris University Hospital Béclère	Paris
France	Paris University Hospital Bicêtre	Paris
France	Paris University Hospital Bichat	Paris
France	Paris University Hospital Jean Verdier	Paris
France	Paris University Hospital La Pitié Salpétrière	Paris
France	Paris University Hospital Louis Mourier	Paris
France	Paris University Hospital Necker	Paris
France	Poissy Hospital CHI Poissy-Saint-Germain	Poissy
France	Pontoise Hospital René Dubos	Pontoise
France	Rennes Private Hospital Clinique Mutualiste La Sagesse	Rennes
France	Rennes University Hospital	Rennes
France	Saint-Grégoire Private Hospital	Rennes
France	Roubaix Hospital	Roubaix
France	Saint-Herblain Private Hospital Polyclinique de l'Atlantique	Saint-Herblain
France	Saint-Mande Army Hospital Begin	Saint-Mande
France	Saint-Martin-d'Hère Private Hospital Clinique Belledonne	Saint-Martin d'Hères
France	Strasbourg Private Hospital Clinique Adassa	Strasbourg
France	Strasbourg University Hospital	Strasbourg
France	Toulouse Private Hospital Clinique Sarrus Teinturiers	Toulouse
France	Toulouse University Hospital	Toulouse
France	Toulouse University Hospital P. DE VIGUIER	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cost / efficiency ratio of the implementation of the generalized neonatal screening of SCID at birth	Efficacy endpoint: number of children receiving early therapeutic suitable for curative ( transplant, enzyme treatment or gene therapy)	18 months
Secondary	Cost / efficiency ratio of the implementation of the generalized neonatal screening of SCID at birth	Efficacy endpoint: life expectancy of children modeled from the results of the study and data from the literature	10 years
Secondary	The cost of care during the first 18 months of life per child enjoying an early curative treatment in the first 4 months of life.	Costs of care will be estimated during the first 18 months of life of the child.	18 months
Secondary	Length of hospitalization of children with SCID in the first 18 months of life		18 months
Secondary	number of avoided deaths		18 months
Secondary	number of detected SCID patients		18 months
Secondary	number of patients detected with other T lymphopenia (SCID variants , DiGeorge , severe T lymphopenia non SCID ... )		18 months
Secondary	number of false negative and false positive results	False negative results : patients from the control group diagnosed with SCID without screening who would have a negative screening or patients from the screening group died from a SCID and with a negative screening False positive: patients from the screening group with a positive screening but without SCID	18 months