Respiratory Distress Syndrome, AdultCOMETSNCT04516486
Coronavirus Studied by Metagenomics in ARDS COVID-19 Patients
An observational study of Respiratory Distress Syndrome, Adult and COVID-19, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Pandemic SARS-CoV-2 (COVID-19) respiratory infection is responsible for more than 4,000 deaths, mainly (67%) secondary to acute respiratory distress syndromes (ARDS). ARDS is usually associated with a mortality of around 40%, but this rate reaches 61% in patients infected with SARS-CoV-2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Distress Syndrome, Adult, COVID-19
- What is being tested?
- retrospective metagenomics on clinical samples collected during hospitalization
- How many people
- 180 participants
- Where
- 1 siteFrance
- Study dates
- 9 Mar 2020to 31 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patient admitted to intensive care for ARDS (Berlin definition) documented at SARS-CoV-2
Who may be able to join
- Patient admitted to intensive care for ARDS (Berlin definition) documented at SARS-CoV-2
- Major patient (age ≥ 18 years)
- Collection of the non-opposition of the patient or his support person, family member or close friend (newsletter)
Who cannot join
- Minor patient
- Refusal to participate in the study
- Patient protected by law
- Prisoner
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Characterization and Prognostic Impact of Inflammatory Responses by Host Transcriptomics and Co-infection by Metagenomics in Patients With ARDS COVID-19 in Intensive Care
Pandemic SARS-CoV-2 (COVID-19) respiratory infection is responsible for more than 4,000 deaths, mainly (67%) secondary to acute respiratory distress syndromes (ARDS). ARDS is usually associated with a mortality of around 40%, but this rate reaches 61% in patients infected with SARS-CoV-2. Two endotypes have been described in patients with ARDS: one, hyper-inflammatory, associated with very high mortality (51%); the second, slightly inflammatory (immunoparalysis), associated with much lower mortality (19%). In COVID-19 patients, distinct immune response profiles have also been observed. Some patients present deep lymphopenia and/or prolonged viral excretions associated with more frequent occurrence of co-infections (+ 29% of virus, + 23% of bacteria, + 10% of fungi). The latter group may be at higher risk in terms of mortality. The intensity of the inflammatory response and/or microbial coinfections therefore appear as risk factors for severity and mortality in patients infected with SARS-CoV-2 which determine the course of the disease. To adapt early optimal therapeutic management to each forms of the disease, it is essential to be able to characterize these profiles on the microbiological and inflammatory level.
With a committed network of 6 intensive-care units across eastern and northern Ile-de-France, 180 patients with ARDS and infected with SARS-CoV-2 are being enrolled. For these patients, a nasopharyngeal swab is collected at inclusion; followed by a new nasopharyngeal swab and a deep respiratory sample once a week, until D28, for an exploration of co-infections and for monitoring the viral load of SARS-CoV-2. The rest of each of these samples are collected for the study. In parallel, the clinical data usually collected in the context of intensive care will be collected on a CRF. They will allow to calculate risk scores such as SOFA.
Read the detailed description
Clinical metagenomics is a technique that has the ability to explore the host's inflammatory response by transcriptomics and the co-infection(s) of all microorganisms. For this, an accredited method according to standard 15189 and used in diagnostic routine for the exploration of complex infections will be used. In practice, the samples will be pre-extracted (chemical, enzymatic and mechanical lysis) then extracted using QiaSymphony (Qiagen). The library will be prepared jointly by Nextera XT kit for DNA and Stranded TruSeq Total RNA (Illumina) then sequenced by NovaSeq (Illumina). The metagenomic and transcriptomic analysis will be performed by our MetaMIC software, supplemented with a specific module recently added for the analysis of SARS-CoV-2 genetic variability and its dynamics over time. Finally, an unsupervised data-mining analysis will be carried out to establish the presence of the "hyperinflammatory" and "immunoparalysis" groups, then allow the analysis of the determinants guiding their clustering. Each group will be analyzed according to its clinical, biological and virological data to determine specific prognostic markers.
The proposed project will therefore comprehensively assess the dynamics of SARS-CoV-2 infection, the inflammatory profile and the microbiological documentation of COVID-19 patients in ARDS by metagenomics / transcriptomics with the aim of detecting profiles of patients at higher risk, to understand the mechanisms of severe forms of the disease and to allow a more precise and earlier evaluation of the prognosis, as well as an adaptation of the management.
- Conditions
- Respiratory Distress Syndrome, Adult, COVID-19
- Being tested
- retrospective metagenomics on clinical samples collected during hospitalization
- Keywords
- Metagenomics, Viral genomic, Transcriptomic, SARS-CoV-2, ARDS
- Medical subject headings
- Respiratory Distress Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
retrospective metagenomics on clinical samples collected during hospitalizationOther
Massive sequencing of respiratory samples (restrospective)
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify two endotypes (hyper-inflammatory and co-infections) and quantify their prognostic value in terms of short-term mortality (Day 28) in patients treated for ARDS infected with SARS-Cov2.
Unsupervised Transcriptomic analysis to explore the presence of 2 different groups of patients in the cohort.
Measured: Day 0 to Day 28 (longitudinal study)
Secondary outcomes (3)
Nature of viral, bacterial and fungal co-infections in the different clusters identified
Shotgun Metagenomics analysis of respiratory samples to explore viruses, bacteria, fungi, parasites in relation with severity of the disease
Measured: Day 0 to Day 28
Comparison of SARS CoV-2 viral replication dynamics in the different clusters identified
Quantification based on metagenomics through time
Measured: Day 0 to Day 28
4. Characterization of the viral genetic determinants selected over time in the different clusters identified
Viral genomic comparison and machine learning to assess the role of the mutations (quasispecies) in the severity of the disease
Measured: Day 0 to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2020
- Study start9 Mar 2020
- Primary completion24 May 2020
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory Distress Syndrome, AdultStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christophe Rodriguez, PharmD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04516486
- Sponsor's protocol ID
- APHP200418
- Acronym
- COMETS
- Status last verified
- Jun 2020
- First submitted
- 23 Jun 2020
- Last updated
- 18 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization and Prognostic Impact of Inflammatory Responses by Host Transcriptomics and Co-infection by Metagenomics in Patients With ARDS COVID-19 in Intensive Care
- ClinicalTrials.gov ID
- NCT04516486
- Acronym / sponsor ID
- COMETS / APHP200418
- Conditions
- Respiratory Distress Syndrome, Adult, COVID-19
- Keywords
- Metagenomics, Viral genomic, Transcriptomic, SARS-CoV-2, ARDS
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 9 Mar 2020 (actual)
- Primary completion
- 24 May 2020 (actual)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 18 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pandemic SARS-CoV-2 (COVID-19) respiratory infection is responsible for more than 4,000 deaths, mainly (67%) secondary to acute respiratory distress syndromes (ARDS). ARDS is usually associated with a mortality of around 40%, but this rate reaches 61% in patients infected with SARS-CoV-2. Two endotypes have been described in patients with ARDS: one, hyper-inflammatory, associated with very high mortality (51%); the second, slightly inflammatory (immunoparalysis), associated with much lower mortality (19%). In COVID-19 patients, distinct immune response profiles have also been observed. Some patients present deep lymphopenia and/or prolonged viral excretions associated with more frequent occurrence of co-infections (+ 29% of virus, + 23% of bacteria, + 10% of fungi). The latter group may be at higher risk in terms of mortality. The intensity of the inflammatory response and/or microbial coinfections therefore appear as risk factors for severity and mortality in patients infected with SARS-CoV-2 which determine the course of the disease. To adapt early optimal therapeutic management to each forms of the disease, it is essential to be able to characterize these profiles on the microbiological and inflammatory level.
With a committed network of 6 intensive-care units across eastern and northern Ile-de-France, 180 patients with ARDS and infected with SARS-CoV-2 are being enrolled. For these patients, a nasopharyngeal swab is collected at inclusion; followed by a new nasopharyngeal swab and a deep respiratory sample once a week, until D28, for an exploration of co-infections and for monitoring the viral load of SARS-CoV-2. The rest of each of these samples are collected for the study. In parallel, the clinical data usually collected in the context of intensive care will be collected on a CRF. They will allow to calculate risk scores such as SOFA.
Detailed description
Clinical metagenomics is a technique that has the ability to explore the host's inflammatory response by transcriptomics and the co-infection(s) of all microorganisms. For this, an accredited method according to standard 15189 and used in diagnostic routine for the exploration of complex infections will be used. In practice, the samples will be pre-extracted (chemical, enzymatic and mechanical lysis) then extracted using QiaSymphony (Qiagen). The library will be prepared jointly by Nextera XT kit for DNA and Stranded TruSeq Total RNA (Illumina) then sequenced by NovaSeq (Illumina). The metagenomic and transcriptomic analysis will be performed by our MetaMIC software, supplemented with a specific module recently added for the analysis of SARS-CoV-2 genetic variability and its dynamics over time. Finally, an unsupervised data-mining analysis will be carried out to establish the presence of the "hyperinflammatory" and "immunoparalysis" groups, then allow the analysis of the determinants guiding their clustering. Each group will be analyzed according to its clinical, biological and virological data to determine specific prognostic markers.
The proposed project will therefore comprehensively assess the dynamics of SARS-CoV-2 infection, the inflammatory profile and the microbiological documentation of COVID-19 patients in ARDS by metagenomics / transcriptomics with the aim of detecting profiles of patients at higher risk, to understand the mechanisms of severe forms of the disease and to allow a more precise and earlier evaluation of the prognosis, as well as an adaptation of the management.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient admitted to intensive care for ARDS (Berlin definition) documented at SARS-CoV-2
Key inclusion criteria (3 listed)
- Patient admitted to intensive care for ARDS (Berlin definition) documented at SARS-CoV-2
- Major patient (age ≥ 18 years)
- Collection of the non-opposition of the patient or his support person, family member or close friend (newsletter)
Key exclusion criteria (4 listed)
- Minor patient
- Refusal to participate in the study
- Patient protected by law
- Prisoner
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| retrospective metagenomics on clinical samples collected during hospitalizationMassive sequencing of respiratory samples (restrospective) | Other | – |
Primary outcome
Identify two endotypes (hyper-inflammatory and co-infections) and quantify their prognostic value in terms of short-term mortality (Day 28) in patients treated for ARDS infected with SARS-Cov2.
Time frame: Day 0 to Day 28 (longitudinal study)
Unsupervised Transcriptomic analysis to explore the presence of 2 different groups of patients in the cohort.
3 secondary outcomes
Nature of viral, bacterial and fungal co-infections in the different clusters identified
Time frame: Day 0 to Day 28
Comparison of SARS CoV-2 viral replication dynamics in the different clusters identified
Time frame: Day 0 to Day 28
4. Characterization of the viral genetic determinants selected over time in the different clusters identified
Time frame: Day 0 to Day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2020.
Related trials for Respiratory Distress Syndrome, Adult
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
Acute Respiratory Distress Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christophe Rodriguez, PharmD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Respiratory Distress Syndrome, Adult and COVID-19, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identify two endotypes (hyper-inflammatory and co-infections) and quantify their prognostic value in terms of short-term mortality (Day 28) in patients treated for ARDS infected with SARS-Cov2. (time frame: Day 0 to Day 28 (longitudinal study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2020.