Clinical Trial: Genetic Autopsy and Sudden Death

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Observational

Official Title: Genetic Autopsy and Sudden Death of Young Subject

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 Summary:

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


Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Comparison of sudden death elucidation rate obtained by high throughput sequencing (NGS) versus conventional autopsy (macroscopic and / or microscopic) [ Time Frame: 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.



Original Primary Outcome: Comparison of sudden death elucidation rate obtained by high throughput sequencing (NGS) versus conventional autopsy (macroscopic and / or microscopic) [ Time Frame: 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).

Determine the rate of sudden death elucidation after conventional autopsy (macroscopic and microscopic) Comparison of sudden death elucidation rate between the two approaches by chi 2 analysis.



Current Secondary Outcome:

  • Describe the epidemiology of causes of sudden death [ Time Frame: 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

  • Comparison of elucidation rates of cause of sudden death including systematic cardiac screening in relatives [ Time Frame: 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 %.

  • Medico-economic modeling of the various diagnostic approaches [ Time Frame: 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


Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: September 7, 2016
Date Started: September 2016
Date Completion: December 2019
Last Updated: October 7, 2016
Last Verified: August 2016