Genetic Autopsy and Sudden Death

Sudden Death Clinical Trial

— AGEMOS  

Official title:

Genetic Autopsy and Sudden Death of Young Subject

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02920203
• Other study ID #: NI 13007
• Status: Recruiting
• Phase: N/A
• First received: September 7, 2016
• Last updated: November 3, 2017
• Start date: October 11, 2017
• Est. completion date: December 2020

Study information

• Verified date: November 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Geoffroy Lorin de la Grandmaison, Pr
• Phone: +33(0)1 47 10 76 90
• Email: g.lorin[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of the study is to better identify hereditary cardiac causes of sudden unexpected death in young subjects through Next-Generation Sequencing of autopsy tissue

Description:

Monitoring :

For index cases group, all the data will be monitored. For the relatives group, only the informed consent will be monitored

Statistical analysis :

• Evaluate the additional elucidation rate of unexpected sudden death

• Evaluate causes obtained by Next Generation Sequencing (NGS) ( in comparison with conventional autopsy (macroscopic and / or microscopic)

• Descriptive study of the causes of sudden unexpected death, identified hereditary cardiac causes percentages compared via various diagnostic approaches

• Cost-effectiveness analysis

Data Management :

A database is created for the AGEMOS study with control of the discrepancies. All the index cases' data entered in the data base will be double checked

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 40 Years

Eligibility

Index cases :

Inclusion Criteria:

• Subjects of more than 2 years old and less than 41 years old

• Sudden unexpected death from natural and nontraumatic causes

• Macroscopic autopsy performed within 72 hours after death and without signs of body decomposition

• No extracardiac obvious causes, including toxicological analysis when available

• No significant coronary cause after autopsy (such as tight coronary stenosis, congenital abnormality of the arteries, coronary vasculitis)

• Informed consent of the close relation (family/reliable person) and / or legal representative

Relatives :

Inclusion Criteria:

• To be a first degree relative (parents, sister, brother, child) of a deceased subject included in the AGEMOS study and accept to perform medical examination and transmit results of examination

Related Conditions & MeSH terms

• Death
• Death, Sudden
• Sudden Death

Intervention

Genetic:
• Heart and spleen tissue
genetic sequencing

Locations

Country	Name	City	State
France	Raymond Poincaré hospital	Garches

Sponsors (7)

Lead Sponsor

Collaborator

Assistance Publique - Hôpitaux de Paris

Cardiogenetic and molecular and cellular myogenetic functionnal unit Pitié Salpêtrière hospital, Paris, Clinical research Unit, Ambroise Paré Hospital, Boulogne Billancourt, Molecular and medical Virology Laboratory, Medical School, Reims, Pathology department and forensic Institute, Raymond Poincaré hospital, Garches, Pitié-Salpêtrière Hospital, Referal Center for Inherited cardiac diseases, Pitié Salpêtrière Hospital, Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of sudden death elucidation rate obtained by high throughput sequencing (NGS) versus conventional autopsy (macroscopic and / or microscopic)	Aim is to determine if elucidation rate of unexpected sudden death causes obtained by high throughput sequencing (NGS) is significantly better than conventional autopsy (macroscopic and / or microscopic) alone.; Inclusion of a series of 100 consecutive and exhaustive cases (index cases) recruited by forensic institutes or pathology departements.; Determine the rate of sudden death elucidation after NGS (after targeted capturing of 100 genes responsible for inherited cardiac diseases, including cardiomyopathy and electrical diseases) and comparison of sudden death elucidation rate obtained with conventional autopsy (macroscopic and microscopic) by chi 2 analysis.	27 months
Secondary	Describe the epidemiology of causes of sudden death	Inclusion of a serie of consecutive and exhaustive subjects recruited by forensic institutes or pathology departements.; Determination all the causes of death after conventional autopsy (unnatural, toxicological, non-cardiovascular, vascular, cardiological and coronary, cardiological and non-coronary causes such as cardiomyopathies & myocarditis, no cause identified Descriptive analysis. All quantitative data will be analyzed with the average, standard deviation and median.; Frequencies and Clopper-Pearson confidence interval of 95% will be provided	27 months
Secondary	Comparison of elucidation rates of cause of sudden death including systematic cardiac screening in relatives	Aim is to determine the impact of systematic family cardiac screening in the understanding of sudden deaths Comparison of elucidation rates of cause of sudden death according to three methods: i) identification of a hereditary heart disease via the systematic cardiac screening performed in relative; ii) by the conventional autopsy; iii) by sequencing NGS analysis; Statistics: test of McNemar (mated series). The threshold for level of statistical significance is chosen at 5 %.	39 months
Secondary	Medico-economic modeling of the various diagnostic approaches	Cost-effectiveness modeling evaluation of medical and economic impact of the genetic molecular autopsy, efficacy being estimated by years of life saved in the family	39 months