Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 12 of 199 for:    Recruiting, Not yet recruiting, Available Studies | Neonatal respiratory distress syndrome

Immune Alveolar Alterations During Pneumonia-Associated Acute Respiratory Distress Syndrome (PICARD2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03971006
Recruitment Status : Not yet recruiting
First Posted : June 3, 2019
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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). 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.


Condition or disease
Acute Respiratory Distress Syndrome

Layout table for study information
Study Type : Observational
Estimated Enrollment : 110 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Immune Alveolar Alterations During Pneumonia-Associated Acute Respiratory Distress Syndrome
Estimated Study Start Date : June 1, 2019
Estimated Primary Completion Date : June 4, 2022
Estimated Study Completion Date : June 28, 2022


Group/Cohort
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.



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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 ]
    Level of expression of PD-1 by alveolar CD8+ lymphocytes

  2. 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 ]
    Level of HLA-DR expression of alveolar monocytes

  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 ]
    Number of days without complication

  4. Determine wether alveolar biomarkers (HLA-DR and PD-1) are potential candidates for immunomodulation [ Time Frame: at day 1 to day 3 ]
    To determine if the level of expression of HLA-DR and PD-1 can be modulated by pharmacological intervention


Biospecimen Retention:   Samples Without DNA
Bronchoalveolar lavage fluid and blood samples (2 heparinized tubes (8 ml) for performing functional tests in the blood compartment and 1 dry 4 ml tube for subsequent cytokine assay (Luminex® analysis) on serum) will be collected in ARDS patients within 48 hours of intubation and in controls.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Group 1 : Immunocompetent Acute Respiratory Distress Syndorme (ARDS) patients Group 2 : Immunosuppressed ARDS patients Group 3 : Controls (no ARDS)
Criteria

Inclusion Criteria:

  • 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))

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))

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03971006


Contacts
Layout table for location contacts
Contact: Nicolas DE PROST, Doctor 01 49 81 23 94 ext 0033 nicolas.de-prost@aphp.fr

Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Layout table for investigator information
Principal Investigator: Nicolas DE PROST Assistance Publique Hôpitaux de Paris - CHU Henri Mondor - Créteil

Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03971006     History of Changes
Other Study ID Numbers: APHP 190092
First Posted: June 3, 2019    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Acute respiratory distress syndrome (ARDS)
Pneumonia
Septic Shock
bronchoalveolar lavage
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Syndrome
Respiratory Tract Diseases
Respiratory Tract Infections
Infant, Newborn, Diseases
Pneumonia
Acute Lung Injury
Disease
Pathologic Processes
Lung Diseases
Respiration Disorders
Infant, Premature, Diseases
Lung Injury