Ignite Creation Date:
2024-05-06 @ 7:24 PM
Last Modification Date:
2024-10-26 @ 3:06 PM
Study NCT ID:
NCT06001645
Status:
RECRUITING
Last Update Posted:
2024-01-17
First Post:
2023-07-31
Brief Title:
Laboratory Biomarkers and Pulmonary Interstitial Emphysema in ARDS PIE-ARDS
Sponsor:
Università Vita-Salute San Raffaele
Organization:
Università Vita-Salute San Raffaele
Study Overview
Official Title:
Pulmonary Interstitial Emphysema Macklin Effect Quantitative Imaging Analysis and CytoKine Profiling to Predict Lung Frailty IN ARDS
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PIE-ARDS
Brief Summary:
Barotrauma pneumothorax pneumomediastinum is a well-described complication of Acute Respiratory Distress Syndrome ARDS especially in patients with coronavirus disease 2019 COVID-19 161 in COVID-19 and about 6 in non-COVID-19 ARDS Macklin effect was recently discovered by our group as an accurate radiological predictor of barotrauma in COVID-19 ARDS the Investigators also found that density histograms automatically extracted from chest CT images provide a reliable insight into lung composition
Since lung frailty is a major issue also in non-COVID-19 ARDS the Investigators want to confirm the predictive role of Macklin effect also in this setting In addition the Investigators aim to explore inflammatory profiling to decipher different biological aspects of the same clinical issue Finally the Investigators want to develop a specific management algorithm for patients diagnosed according to our findings with a specific ARDS sub phenotype characterized by increased lung frailty
Since lung frailty is a major issue also in non-COVID-19 ARDS the Investigators want to confirm the predictive role of Macklin effect also in this setting In addition the Investigators aim to explore inflammatory profiling to decipher different biological aspects of the same clinical issue Finally the Investigators want to develop a specific management algorithm for patients diagnosed according to our findings with a specific ARDS sub phenotype characterized by increased lung frailty
Detailed Description:
Barotrauma occurs frequently in acute respiratory distress syndrome ARDS and has a difficult non-standardized management Unfortunately mortality rates remain high 60 in COVID-19 ARDS around 46 in non-COVID-19 ARDS Interestingly data from COVID-19 patients suggested that barotrauma may occur also in spontaneously breathing patients with ARDS Accordingly frailty of lung parenchyma represents a major issue in ARDS Protective mechanical ventilation ie ventilation with low tidal volume and low airway pressures remains a cornerstone of supportive management of ARDS Unfortunately mechanical ventilation may worsen pulmonary damage ventilator-induced lung injury and in high-risk patients may induce barotrauma even when ventilator settings are maintained within the safe limit of protective ARDS Early identification of high-risk features could therefore allow clinicians to individualize management of high-risk patients by tailoring respiratory support and potentially select candidates for advanced support ie extracorporeal membrane oxygenation before development of overt barotrauma
Macklin effect is a well-described radiological sign originally intended to differentiate between peripheral distal airway rupture respiratory barotrauma and central lesion to large airwaysesophaegal injury causes of air leakage in the mediastinum However the Investigators recently identified Macklin effect as a strong radiological predictor of barotrauma development in mechanically ventilated COVID-19 ARDS patients sensitivity 892 specificity 956 In our cohort radiologically-detected Macklin effect was identified 8-12 days before development of pneumomediastinumpneumothorax These preliminary results have been confirmed in a subsequent multicenter study sample size 697 patients sensitivity 100 specificity 998
Furthermore preliminary data suggest that early application of awake venovenous extracorporeal membrane oxygenation ECMO before invasive mechanical ventilation in COVID-19 patients with severe ARDS and at high-risk for barotrauma defined as presence of Macklin effect on chest CT imaging might result in no barotrauma events with a low intubation rate
Concurrently a hyper inflammatory sub phenotype has been associated with overall worse outcome both in terms of mortality and ventilator-free days in ARDS Moreover the occurrence of lung injury during mechanical ventilation has been proven to be significantly related to the recruitment of mast cells via CXCL10CXCR3 signaling
In this view confirmation of Macklin effect predictive role and identification of further novel laboratory biomarkers could provide instruments for early risk stratification in ARDS patients
Taken together i quantitative imaging analysis and ii systemic inflammatory profiling could decipher different biological aspects of the same clinical issue possibly laying foundation for the definition of a multimodality signature of lung frailty in ARDS patients
Accordingly the driving hypotheses of this retrospectiveprospective study is that identification of a novel ARDS sub phenotype characterized irrespective of the underlying etiology by increased lung frailty could substantially improve the poor prognosis routinely associated with this condition possibly being a landmark for personalized management strategies
To further validate the role of Macklin effect the Investigators will
evaluate the accuracy of Macklin effect in a retrospective cohort of 350 ARDS patients COVID-19 and non-COVID-19
identify throughout densitometry machine learning and artificial intelligence-based approaches novel imaging biomarkers characteristics of higher lung frailty in the same cohort
In the main prospective study the Investigators will
analyse the following biomarkers in the serum and bronchoalveolar lavage fluid of 100 ARDS patients prospectively enrolled Interleukin-8 IL-8 Interleukin IL-6 IL-1Ra IL-18 interferon IFN Angiopoietin-2 Ang-2 Tumour Necrosis Factor receptor-1 TNFr1 Plasminogen Activator Inhibitor-1PAI-1 Receptor for Advanced Glycation Endproducts RAGE Intercellular adhesion molecule-1 ICAM-1 Surfactant Protein D SPD protein C Von Willebrand Factor VWF CXCL10CXCR3 and metalloproteases MMP9 MMP10
Develop a specific management algorithm for ARDS patients at high risk for barotrauma by collecting clinical and outcome data from 10 ARDS patients receiving unconventional management eg awake ECMO ultraprotective ventilation etc
Macklin effect is a well-described radiological sign originally intended to differentiate between peripheral distal airway rupture respiratory barotrauma and central lesion to large airwaysesophaegal injury causes of air leakage in the mediastinum However the Investigators recently identified Macklin effect as a strong radiological predictor of barotrauma development in mechanically ventilated COVID-19 ARDS patients sensitivity 892 specificity 956 In our cohort radiologically-detected Macklin effect was identified 8-12 days before development of pneumomediastinumpneumothorax These preliminary results have been confirmed in a subsequent multicenter study sample size 697 patients sensitivity 100 specificity 998
Furthermore preliminary data suggest that early application of awake venovenous extracorporeal membrane oxygenation ECMO before invasive mechanical ventilation in COVID-19 patients with severe ARDS and at high-risk for barotrauma defined as presence of Macklin effect on chest CT imaging might result in no barotrauma events with a low intubation rate
Concurrently a hyper inflammatory sub phenotype has been associated with overall worse outcome both in terms of mortality and ventilator-free days in ARDS Moreover the occurrence of lung injury during mechanical ventilation has been proven to be significantly related to the recruitment of mast cells via CXCL10CXCR3 signaling
In this view confirmation of Macklin effect predictive role and identification of further novel laboratory biomarkers could provide instruments for early risk stratification in ARDS patients
Taken together i quantitative imaging analysis and ii systemic inflammatory profiling could decipher different biological aspects of the same clinical issue possibly laying foundation for the definition of a multimodality signature of lung frailty in ARDS patients
Accordingly the driving hypotheses of this retrospectiveprospective study is that identification of a novel ARDS sub phenotype characterized irrespective of the underlying etiology by increased lung frailty could substantially improve the poor prognosis routinely associated with this condition possibly being a landmark for personalized management strategies
To further validate the role of Macklin effect the Investigators will
evaluate the accuracy of Macklin effect in a retrospective cohort of 350 ARDS patients COVID-19 and non-COVID-19
identify throughout densitometry machine learning and artificial intelligence-based approaches novel imaging biomarkers characteristics of higher lung frailty in the same cohort
In the main prospective study the Investigators will
analyse the following biomarkers in the serum and bronchoalveolar lavage fluid of 100 ARDS patients prospectively enrolled Interleukin-8 IL-8 Interleukin IL-6 IL-1Ra IL-18 interferon IFN Angiopoietin-2 Ang-2 Tumour Necrosis Factor receptor-1 TNFr1 Plasminogen Activator Inhibitor-1PAI-1 Receptor for Advanced Glycation Endproducts RAGE Intercellular adhesion molecule-1 ICAM-1 Surfactant Protein D SPD protein C Von Willebrand Factor VWF CXCL10CXCR3 and metalloproteases MMP9 MMP10
Develop a specific management algorithm for ARDS patients at high risk for barotrauma by collecting clinical and outcome data from 10 ARDS patients receiving unconventional management eg awake ECMO ultraprotective ventilation etc
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None