Genetic Autopsy and Sudden Death (AGEMOS)

Genetic Autopsy and Sudden Death of Young Subject

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

Study Overview

• Status: Unknown
• Conditions: Sudden Death
• Intervention / Treatment: Genetic: Heart and spleen 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 Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• France
  • Garches, France, 92380
    • Recruiting
    • Raymond Poincaré Hospital
    • Contact: Geoffroy Lorin de la Grandmaison, Pr; Phone Number: +33(0)1 47 10 76 90; Email: g.lorin@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 40 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Index cases enrolled: series of consecutive and exhaustive cases recruited by forensic institutes or pathology departements Relatives enrolled: as many as possible during the recruitment period

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
index cases group; unexpected sudden death cases recruited by forensic institutes or pathology departements	Genetic: Heart and spleen tissue; genetic sequencing
first degree relatives group; Relatives enrolled of unexpected sudden death index cases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Pitié-Salpêtrière Hospital; Pathology department and forensic Institute, Raymond Poincaré hospital, Garches; Referal Center for Inherited cardiac diseases, Pitié Salpêtrière Hospital, Paris; Clinical research Unit, Ambroise Paré Hospital, Boulogne Billancourt; Cardiogenetic and molecular and cellular myogenetic functionnal unit Pitié Salpêtrière hospital, Paris; Molecular and medical Virology Laboratory, Medical School, Reims
• Investigators: Principal Investigator: Geoffroy Lorin de la Grandmaison, Pr, Assistance Publique Hoptiaux de Paris; Study Director: Philippe Charron, MD, PhD, +33 (0)1 42 16 13 47

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 11, 2017
• Primary Completion (ANTICIPATED): September 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: September 7, 2016
• First Submitted That Met QC Criteria: September 28, 2016
• First Posted (ESTIMATE): September 30, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 3, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: sequencing; Sudden unexpected death; young subjects; molecular genetic autopsy
• Additional Relevant MeSH Terms: Pathologic Processes; Death; Death, Sudden
• Other Study ID Numbers: NI 13007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO