Pathological Findings of Fatal COVID-19 (HISTOCOVID)

November 29, 2023 updated by: Nantes University Hospital

Pathological Findings in Critically-ill Patients Who Died From SARS-CoV-2 Related Acute Respiratory Distress Syndrome

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new coronavirus discovered in December 2019 in Wuhan, China and currently responsible of a worldwide outbreak and the death of more than 55,000 patients in France. The more severe form of COVID-19 disease induces a pneumonia with profound hypoxemia which may require invasive mechanical ventilation. It is estimated that 5% of COVID-19 patients are admitted to the Intensive Care Unit (ICU) for management. Hospital mortality in patients who develop severe acute respiratory distress syndrome (ARDS) ranges between 40% and 60%. The investigators purpose to investigate the pathological findings of COVID-19 patients who died from ARDS in the ICU by doing post-mortem lung biopsies

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Forty-four French ICUs participate to this study with the aim to perform 200 lung biopsies in 100 patients over a 12-month period. This cohort will be the largest pathological database of COVID-19 patients who developed ARDS. In accordance with the French law, this study has been approved and registered by the French Agency of Biomedicine and the French Ministry of Education and Research (#PFS 20-016). Two transcutaneous lung biopsies per patient will be performed using a 14G needle and anatomical landmarks (1 anterior biopsy and 1 posterior biopsy). All biopsies will be referred to the Department of Pathology of Nantes university hospital and analysed by a group of pathologists specialized in lung tissue. The primary objective is to describe and characterize the lesions of the lung induced by the SARS-CoV-2 infection. The secondary objectives are to correlate the pathological findings with the patients' demographics, the treatments administered during the ICU stay, the ventilator settings, to document the percentage of co-infections and their types, compare the radiographic findings (Chest X-ray and CT-scan of the chest) with the pathological findings, to compare the pathological findings of early deaths (<1week after ICU admission) versus late deaths (>1 week). These pathological findings will undoubtedly help to better understand the pathophysiology of SARS-CoV-2 pneumonia and pave the way to the development of new therapeutic strategies

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
170

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Amiens, France
        • CH Amiens
      • Angers, France
        • Angers University hospital
      • Angoulême, France
        • CH Angoulème
      • Annecy, France
        • CH Annecy
      • Antony, France
        • Hôpital Privé d'Antony
      • Argenteuil, France
        • CH Argenteuil
      • Belfort, France
        • Ch Belfort
      • Bordeaux, France
        • CHU Bordeaux
      • Bry-sur-Marne, France
        • Hopital Sainte Camille
      • Cahors, France
        • CH Cahors
      • Cergy-Pontoise, France
        • CH Cergy Pontoise
      • Cholet, France
        • CH Cholet
      • Clermont-Ferrand, France
        • CHU Clermont-Ferrand
      • Compiègne, France
        • CH Compiègne-Noyon
      • La Roche-sur-Yon, France
        • CHD Vendee
      • Lyon, France
        • Hopital Lyon Sud
      • Marseillette, France
        • Marseille Hopital Nord APHM
      • Melun, France
        • CH Melun
      • Montélimar, France
        • CH Montélimar
      • Nantes, France, 44000
        • Nantes University Hospital
      • Nice, France
        • CHU Nice
      • Orléans, France
        • CHR Orléans
      • Paris, France
        • CH Ambroise Paré APHP
      • Paris, France
        • GHEF Marne La Vallée
      • Paris, France
        • Hopital Antoine Béclère APHP
      • Paris, France
        • Hôpital Cochin APHP
      • Paris, France
        • Hopital Georges Pompidou APHP
      • Paris, France
        • Hopital La Pitié Salpetrière APHP
      • Paris, France
        • Hopital Louis Mourier APHP
      • Paris, France
        • Hopital Necker APHP
      • Paris, France
        • Hopital Saint-Antoine APHP
      • Paris, France
        • Hôpital Saint-Louis APHP
      • Poissy, France
        • CH Poissy
      • Quincy-sous-Sénart, France
        • Hôpital Privé Claude Galien
      • Reims, France
        • CH Reims
      • Rennes, France
        • CHU Rennes
      • Saint-Brieuc, France
        • CH Saint-Brieuc
      • Saint-Étienne, France
        • CHU Saint-Etienne
      • Suresnes, France
        • Hopital Foch
      • Tours, France
        • Chru Tours
      • Troyes, France
        • CH Troyes
      • Vannes, France
        • CH Vannes
      • Versailles, France
        • CH Versailles

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients deceased in the ICU from a Covid-19 during the study period

Description

Inclusion Criteria:

  • Adult patients (Age≥18 years-old)
  • Hospitalized in Intensive Care Unit (ICU)
  • Dead in the ICU from documented Covid-19 (clinical and radiological signs of pneumonia with a positive SARS-Cov-2 PCR from the upper or lower respiratory tract)
  • Not registered in the national register of refusal of the French Biomedicine Agency
  • According to French law, there was no requirement for signed consent, but the patient's next of kin were informed about the study before enrolment and were given a letter of information about the study.

Exclusion Criteria:

  • Covid-19 not documented by a positive SARS-Cov-2 PCR
  • Patient with a positive SARS-Cov-2 PCR but without any signs of pneumonia during the ICU stay (no clinical and no radiological signs of pneumonia)
  • Patient registered in the "national register of refusal" of the French Biomedicine Agency
  • Refusal expressed by the patient's next of kin to participate to the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Critically-ill adult patients who died in the Intensive Care Unit from a documented COVID-19
Other: 2 post-mortem transcutaneous lung biopsies (1 anterior ; 1 posterior) using anatomical landmarks
All specimens are fixed with 4% neutral formaldehyde and embedded in paraffin wax in the department of pathology of each participating centre. Afterwards, all samples are sent for analysis to the department of pathology of Nantes university hospital. All biopsies are independently analysed by a group of pathologists who are experts in lung tissue and blinded to clinical information. All biopsies will be analysed using a predetermined semi-quantitative histological scoring grid. The pathologists are asked to assess the degree of: edema, cell necrosis, hyaline membrane formation, proliferation of alveolar type 2 cells, fibrosis, capillary congestion, alveolar edema, neutrophilic infiltration, and microscopic thrombosis. Finally, the following patterns are recorded: exudative diffuse alveolar damage (DAD), proliferative DAD, fibrosis, intra-alveolar haemorrhage, lymphocytic pneumonia, organizing pneumonia, acute fibrinous organizing pneumonia (AFOP), thrombotic microangiopathy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Analysis of the pathological findings of a large cohort of patients who died from COVID-19 in the ICU
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Detailed description and analysis of the primary lesions of the lungs in patients who died in the ICU from Covid-19.
Two post-mortem lung biopsies performed immediately after death.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparison between early (<1 week after ICU admission) and late (≥1 week) deaths
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Comparison of pathological findings according to the time between ICU admission and death.
Two post-mortem lung biopsies performed immediately after death.
Analysis of the influence of ARDS severity and length on pathological findings
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Comparison of pathological findings according to the length of acute respiratory syndrome.
Two post-mortem lung biopsies performed immediately after death.
Analysis of the influence of ARDS severity and length on pathological findings
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Comparison of pathological findings according to the duration of acute respiratory syndrome.
Two post-mortem lung biopsies performed immediately after death.
Analysis of the influence of pharmacological treatments (steroids) on pathological findings
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Comparison of pathological findings between patients who received steroids and those who did not.
Two post-mortem lung biopsies performed immediately after death.
Analysis of the correlation between radiological findings and pathological findings
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Comparison between radiological description of the CT of the lungs and the radiological findings.
Two post-mortem lung biopsies performed immediately after death.
Association between the primary cause of death and pathological findings
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Analysis of the pathological findings according to the primary cause of death (hypoxia, shock, hypoxia and shock, cardiac arrest, other).
Two post-mortem lung biopsies performed immediately after death.
Analysis of the correlation between the ventilator settings and pathological findings
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Analysis of the correlation between the ventilator settings (tidal volume, PEEP, driving pressure, plateau pressure, static compliance, volume or pressure mode) and pathological findings.
Two post-mortem lung biopsies performed immediately after death.
Co-infections
Time Frame: Two post-mortem lung biopsies performed immediately after death.
Description of the co-infection (bacterial or fungal infections) documented by pathological findings
Two post-mortem lung biopsies performed immediately after death.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nantes University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Research Agency, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 22, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 3, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 3, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 15, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 19, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 30, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 29, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MR_HISTOCOVID

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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