Genetic Autopsy and Sudden Death

• Conditions: Sudden Death
• Interventions: Genetic: Heart and spleen tissue

• Registration Number: NCT02920203
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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

Detailed 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

Study Timeline

• Study First Submitted: 2016-09-07
• Study First Submitted QC: 2016-09-28
• Study First Posted: 2016-09-30
• Study Start: 2017-10-11
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-03
• Last Update Posted: 2017-11-06
• Primary Completion: 2020-09
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
index cases group	Heart and spleen tissue	unexpected sudden death cases recruited by forensic institutes or pathology departements

Primary Outcome Measures

Name	Time	Method
Comparison of sudden death elucidation rate obtained by high throughput sequencing (NGS) versus conventional autopsy (macroscopic and / or microscopic)	27 months	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.

Secondary Outcome Measures

Name	Time	Method
Comparison of elucidation rates of cause of sudden death including systematic cardiac screening in relatives	39 months	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 %.
Describe the epidemiology of causes of sudden death	27 months	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
Medico-economic modeling of the various diagnostic approaches	39 months	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

Trial Locations

Locations (1)

Raymond Poincaré hospital; 🇫🇷 Garches, France