Acute Respiratory Distress SyndromePICARD2NCT03971006
Immune Alveolar Alterations During Pneumonia-Associated Acute Respiratory Distress Syndrome
An observational study of Acute Respiratory Distress Syndrome, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Sepsis is a dysregulated host response to severe life-threatening infections, leading to organ failure and death in up to 40% of patients with septic shock. Pulmonary infections are the main cause of community-acquired sepsis and frequently lead to the development of acute respiratory distress syndrome(ARDS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- How many people
- 110 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2019to 28 Jun 2022
- 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: Group 1 : Immunocompetent Acute Respiratory Distress Syndorme (ARDS) patients Group 2 : Immunosuppressed ARDS patients Group 3 : Controls (no ARDS)
Who may be able to join
- Age ≥ 18 years
- Affiliated to a social security system
- Patient informed and have given his non opposition verbally (trustworthy or a family member non opposition is required if the patient is unable to give his non opposition)
- Groupe 1 :
- Patient with ARDS secondary to pneumonia defined by following criteria: Intubation and mechanical ventilation for less than 48 hours Lung infection evolving since less than 7 days Bilateral pulmonary radiological opacities compatible with edema pulmonary lesion PaO2 / FiO2 ratio ≤ 300 mmHg with a positive expiratory pressure level ≥ 5 cmH2O
- Absence of immunosuppression (No HIV infection, bone marrow or solid organ transplantation, post-chemotherapy aplasia, immunosuppressive therapy or corticosteroid therapy (>200 mg / day of hydrocortisone or equivalent in the 4 weeks prior to inclusion))
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- Group 2 - Patient with ARDS secondary to pneumonia defined by following criteria: Intubation and mechanical ventilation for less than 48 hours Lung infection evolving since less than 7 days Bilateral pulmonary radiological opacities compatible with edema pulmonary lesion PaO2 / FiO2 ratio ≤ 300 mmHg with a positive expiratory pressure level ≥ 5 cmH2O
- Previously known immunosuppression (patient with HIV, solid tumor, solid organ transplantation or under corticosteroids therapy since at least 4 weeks before inclusion)
- Group 3
- LBA indicated in usual care
- Absence of ARDS
- Absence of evolutionary infection
- Absence of infiltrative lung disease
- Absence of immunosuppression (No HIV infection, bone marrow or solid organ transplantation, post-chemotherapy aplasia, immunosuppressive therapy, corticosteroid therapy (> 200 mg / day of hydrocortisone or equivalent in the 4 weeks prior to inclusion))
Who cannot join
- Chronic respiratory insufficiency treated by long-term oxygen therapy and / or long-term respiratory assistance
- Child-Pugh C cirrhosis
- Pulmonary fibrosis
- Active lymphoid and myeloid malignant hemopathies
- Neutropenia (neutrophils <1500 / mm3)
- Patient moribund the day of inclusion or having an IGS II score greater than 90
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- Irreversible neurological pathology: cerebral involvement, encephalic death
- Decision to limit active therapies
- Deep hypoxemia (PaO2 / FiO2 <75 mmHg)
- Patient protected by law
- Pregnant or lactating woman
Trial locations and contacts
No sites are listed yet.
About this study
Sepsis is a dysregulated host response to severe life-threatening infections, leading to organ failure and death in up to 40% of patients with septic shock. Pulmonary infections are the main cause of community-acquired sepsis and frequently lead to the development of acute respiratory distress syndrome(ARDS). Features of immunosuppression, including diminished cell surface monocyte human leukocyte antigen DR (mHLA-DR) expression, are strongly associated with hospital mortality. Such decrease in HLA-DR expression on antigen-presenting cells has been associated with impairment of microbial antigens to Tcells. Septic patients also show elevated expression of inhibitory receptors associated with cell exhaustion.. Yet, biochemical, flow cytometric and immunohistochemical findings consistent with immunosuppression have been observed in lungs and spleen of patients died of sepsis and multiple organ failure, demonstrating the relevance of studying these defects directly in organ tissues. A novel approach aimed to characterize the role and prognostic value of alveolar biomarkers measured directly in the injured lungs is warranted and supported by: -disappointing results of previous clinical trials attempting to restore the level of biomarkers measured on circulating cells; -evidences of regional immunosuppression in lungs of ARDS patients; -lung is the main site of hospital-acquired infections with a prevalence of ventilator-associated pneumonia in 30% over the course of Intensive Care Unit(ICU) stay in ARDS patients.
Investigators speculate that biomarkers measured on alveolar leukocytes (AL) surface, are important predictors of outcome and potential therapeutic targets in ICU patients with pneumonia-associated ARDS.
Read more
Investigators aim to explore whether biomarkers measured directly on AL from patients with pneumonia-associated ARDS are associated to regional pulmonary immunosuppression using leukocyte functional tests; and predictors of outcomes.
Bronchoalveolar lavage fluid(BALF) and blood samples will be collected in ARDS patients. Leukocyte populations and cell membrane biomarkers will be quantified using flow cytometry. Leukocyte functional tests will be performed ex vivo on leukocytes collected from BALF and blood samples. Pharmacological interventions will be performed ex vivo.
This project aims to identify biomarkers associated with outcomes and potential therapeutic targets.
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Acute respiratory distress syndrome (ARDS), Pneumonia, Septic Shock, bronchoalveolar lavage
- Medical subject headings
- Respiratory Distress Syndrome, Pneumonia, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Immunocompetent ARDS patients | (n=50) Patients with moderate-to-severe pneumonia-associated Acute Respiratory Distress Syndorme (ARDS) and no immunosuppression (excluding patients with HIV infection, solid tumor or hematological malignancies, organ transplant or taking steroids since more than 4 weeks). | |
| Immunosuppressed ARDS patients | (n=50) Patients with moderate-to-severe pneumonia-associated Acute Respiratory Distress Syndorme (ARDS) (Berlin definition (2)) and previously known immunosuppression (as listed above). These patients will allow comparing the cell defects observed in the study population to those observed in immunosuppressed patients. | |
| Controls | (n=10) Patients undergoing a bronchoscopy with Bronchoalveolar Liquid (BAL) as part of routine care but having neither ARDS nor active lung infection, infiltrating lung disease or immunosuppression. These patients will allow quantifying normal levels of the studied biomarkers in the alveolar and blood compartments. |
What is being measured
The primary outcome is the main question the study is designed to answer.
HLA-DR expression level of alveolar monocytes at the early phase of infectious Acute Respiratory Distress Syndrome (ARDS)
Measurement by flow cytometry phagocytosis and TNF-α synthesis of alveolar monocytes in immunocompetent patients, compared to immunocompromised patients
Measured: at day 1 to day 3
Secondary outcomes (4)
Impact of the level of expression of PD-1 by alveolar CD8 + lymphocytes on their function during septic ARDS in immunocompetent and immunocompromised patients.
Level of expression of PD-1 by alveolar CD8+ lymphocytes
Measured: at day 1 to day 3
Comparaison of the level of HLA-DR expression of alveolar monocytes between immunocompetent and immunosuppressed patients being managed for septic ARDS.
Level of HLA-DR expression of alveolar monocytes
Measured: at day 1 to day 3
Link between the alveolar monocyte HLA-DR expression level and the prognosis of immunocompetent and immunosuppressed patients being managed for septic ARDS.
Number of days without complication
Measured: day 28
Determine wether alveolar biomarkers (HLA-DR and PD-1) are potential candidates for immunomodulation
To determine if the level of expression of HLA-DR and PD-1 can be modulated by pharmacological intervention
Measured: at day 1 to day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2019
- Study start1 Jun 2019 (estimated)
- Primary completion4 Jun 2022 (estimated)
- Study completion28 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies 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
- Other
- Time perspective
- Prospective
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas DE PROST, Principal investigator, Assistance Publique Hôpitaux de Paris - CHU Henri Mondor - Créteil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03971006
- Sponsor's protocol ID
- APHP 190092
- Acronym
- PICARD2
- Status last verified
- May 2019
- First submitted
- 29 May 2019
- Last updated
- 3 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Alveolar Alterations During Pneumonia-Associated Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT03971006
- Acronym / sponsor ID
- PICARD2 / APHP 190092
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Acute respiratory distress syndrome (ARDS), Pneumonia, Septic Shock, bronchoalveolar lavage
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Jun 2019 (estimated)
- Primary completion
- 4 Jun 2022 (estimated)
- Study completion
- 28 Jun 2022 (estimated)
- First posted
- 3 Jun 2019 (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.
Sepsis is a dysregulated host response to severe life-threatening infections, leading to organ failure and death in up to 40% of patients with septic shock. Pulmonary infections are the main cause of community-acquired sepsis and frequently lead to the development of acute respiratory distress syndrome(ARDS). Features of immunosuppression, including diminished cell surface monocyte human leukocyte antigen DR (mHLA-DR) expression, are strongly associated with hospital mortality. Such decrease in HLA-DR expression on antigen-presenting cells has been associated with impairment of microbial antigens to Tcells. Septic patients also show elevated expression of inhibitory receptors associated with cell exhaustion.. Yet, biochemical, flow cytometric and immunohistochemical findings consistent with immunosuppression have been observed in lungs and spleen of patients died of sepsis and multiple organ failure, demonstrating the relevance of studying these defects directly in organ tissues. A novel approach aimed to characterize the role and prognostic value of alveolar biomarkers measured directly in the injured lungs is warranted and supported by: -disappointing results of previous clinical trials attempting to restore the level of biomarkers measured on circulating cells; -evidences of regional immunosuppression in lungs of ARDS patients; -lung is the main site of hospital-acquired infections with a prevalence of ventilator-associated pneumonia in 30% over the course of Intensive Care Unit(ICU) stay in ARDS patients.
Investigators speculate that biomarkers measured on alveolar leukocytes (AL) surface, are important predictors of outcome and potential therapeutic targets in ICU patients with pneumonia-associated ARDS.
Investigators aim to explore whether biomarkers measured directly on AL from patients with pneumonia-associated ARDS are associated to regional pulmonary immunosuppression using leukocyte functional tests; and predictors of outcomes.
Bronchoalveolar lavage fluid(BALF) and blood samples will be collected in ARDS patients. Leukocyte populations and cell membrane biomarkers will be quantified using flow cytometry. Leukocyte functional tests will be performed ex vivo on leukocytes collected from BALF and blood samples. Pharmacological interventions will be performed ex vivo.
This project aims to identify biomarkers associated with outcomes and potential therapeutic targets.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Immunocompetent ARDS patients | – | –(n=50) Patients with moderate-to-severe pneumonia-associated Acute Respiratory Distress Syndorme (ARDS) and no immunosuppression (excluding patients with HIV infection, solid tumor or hematological malignancies, organ transplant or taking steroids since more than 4 weeks). |
| Immunosuppressed ARDS patients | – | –(n=50) Patients with moderate-to-severe pneumonia-associated Acute Respiratory Distress Syndorme (ARDS) (Berlin definition (2)) and previously known immunosuppression (as listed above). These patients will allow comparing the cell defects observed in the study population to those observed in immunosuppressed patients. |
| Controls | – | –(n=10) Patients undergoing a bronchoscopy with Bronchoalveolar Liquid (BAL) as part of routine care but having neither ARDS nor active lung infection, infiltrating lung disease or immunosuppression. These patients will allow quantifying normal levels of the studied biomarkers in the alveolar and blood compartments. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Group 1 : Immunocompetent Acute Respiratory Distress Syndorme (ARDS) patients Group 2 : Immunosuppressed ARDS patients Group 3 : Controls (no ARDS)
Key inclusion criteria (14 listed)
- Age ≥ 18 years
- Affiliated to a social security system
- Patient informed and have given his non opposition verbally (trustworthy or a family member non opposition is required if the patient is unable to give his non opposition)
- Patient with ARDS secondary to pneumonia defined by following criteria: Intubation and mechanical ventilation for less than 48 hours Lung infection evolving since less than 7 days Bilateral pulmonary radiological opacities compatible with edema pulmonary lesion PaO2 / FiO2 ratio ≤ 300 mmHg with a positive expiratory pressure level ≥ 5 cmH2O
- Absence of immunosuppression (No HIV infection, bone marrow or solid organ transplantation, post-chemotherapy aplasia, immunosuppressive therapy or corticosteroid therapy (>200 mg / day of hydrocortisone or equivalent in the 4 weeks prior to inclusion))
Key exclusion criteria (11 listed)
- Chronic respiratory insufficiency treated by long-term oxygen therapy and / or long-term respiratory assistance
- Child-Pugh C cirrhosis
- Pulmonary fibrosis
- Active lymphoid and myeloid malignant hemopathies
- Neutropenia (neutrophils <1500 / mm3)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
HLA-DR expression level of alveolar monocytes at the early phase of infectious Acute Respiratory Distress Syndrome (ARDS)
Time frame: at day 1 to day 3
Measurement by flow cytometry phagocytosis and TNF-α synthesis of alveolar monocytes in immunocompetent patients, compared to immunocompromised patients
4 secondary outcomes
Impact of the level of expression of PD-1 by alveolar CD8 + lymphocytes on their function during septic ARDS in immunocompetent and immunocompromised patients.
Time frame: at day 1 to day 3
Comparaison of the level of HLA-DR expression of alveolar monocytes between immunocompetent and immunosuppressed patients being managed for septic ARDS.
Time frame: at day 1 to day 3
Link between the alveolar monocyte HLA-DR expression level and the prognosis of immunocompetent and immunosuppressed patients being managed for septic ARDS.
Time frame: day 28
Determine wether alveolar biomarkers (HLA-DR and PD-1) are potential candidates for immunomodulation
Time frame: at day 1 to day 3
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2019.
- Individual participant dataSharing planned: No. DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
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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.
Nicolas DE PROST principal investigator
Assistance Publique Hôpitaux de Paris - CHU Henri Mondor - Créteil
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Respiratory Distress Syndrome, run by Assistance Publique - Hôpitaux de Paris.
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 14 inclusion and 11 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 3 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Contact Nicolas DE PROST, Doctor (01 49 81 23 94 ext. 0033, nicolas.de-prost@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HLA-DR expression level of alveolar monocytes at the early phase of infectious Acute Respiratory Distress Syndrome (ARDS) (time frame: at day 1 to day 3). 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 3 Jun 2019.