Acute Respiratory Distress SyndromePIE-ARDSNCT06001645
Laboratory Biomarkers and Pulmonary Interstitial Emphysema in ARDS (PIE-ARDS)
An observational study of Acute Respiratory Distress Syndrome and Barotrauma, run by Università Vita-Salute San Raffaele at 4 sites in Italy.
Trial summary
Barotrauma (pneumothorax, pneumomediastinum) is a well-described complication of Acute Respiratory Distress Syndrome (ARDS), especially in patients with coronavirus disease 2019 (COVID-19) (16.1% in COVID-19, and about 6% in non-COVID-19 ARDS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Barotrauma
- What is being tested?
- Blood and bronchoalveolar fluid collection and analysis and Chest CT scan
- How many people
- 110 participants
- Where
- 4 sitesItaly
- Study dates
- 27 Nov 2023to Jul 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: Patients with ARDS diagnosis will be enrolled. With the exception of blood and BAL samples collection, all patients enrolled in the prospective cohort will follow their normal course of diagnosis/treatment without any further requirements for the scope of this study other than those provided in the normal management of patients with this condition. Furthermore, any decision regarding drug or procedure will be made by the physician based on her/his clinical judgment, independently from the decision to include the patient in this study. No follow-up medical and/or imaging examinations/laboratory analysis after hospital discharge are needed by the present study design.
Who may be able to join
- Clinical and radiological signs of ARDS, according to Berlin criteria, requiring ICU admission;
- Obtain duly signed informed consent
- Availability of at least one chest CT scan during hospital stay
Who cannot join
- Poor quality imaging (because of motion/respiratory artefacts).
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy4 sites, 4 recruiting
- Not yet recruiting
A.O.U. di Cagliari
Cagliari
Gabriele Finco, MD
- Recruiting
IRCCS San Raffaele Scientific Institute
Milan, 20132
Diego Palumbo, MD, 0039022643 ext. 6151, palumbo.diego@hsr.it
Alessandro Belletti, MD, 0039022643 ext. 6151, belletti.alessandro@hsr.it
- Not yet recruiting
A.O.U. Pisana
Pisa
Fabio Guarracino, MD
- Not yet recruiting
Ospedale San Carlo
Potenza
Gianluca Paternoster, MD
About this study
Official title: Pulmonary Interstitial Emphysema (Macklin Effect), Quantitative Imaging Analysis and CytoKine Profiling to Predict Lung Frailty IN ARDS
Barotrauma (pneumothorax, pneumomediastinum) is a well-described complication of Acute Respiratory Distress Syndrome (ARDS), especially in patients with coronavirus disease 2019 (COVID-19) (16.1% 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
Read the 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 (i.e. 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 (i.e. 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 airways/esophaegal 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: 89.2%; specificity: 95.6%). In our cohort, radiologically-detected Macklin effect was identified 8-12 days before development of pneumomediastinum/pneumothorax. These preliminary results have been confirmed in a subsequent multicenter study (sample size 697 patients; sensitivity: 100%; specificity: 99.8%).
Furthermore, preliminary data suggest that early application of awake veno/venous 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 CXCL10/CXCR3 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 retrospective/prospective 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-1(PAI-1), Receptor for Advanced Glycation Endproducts (RAGE), Intercellular adhesion molecule-1 (ICAM-1), Surfactant Protein D (SPD), protein C, Von Willebrand Factor (VWF), CXCL10/CXCR3, 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 (e.g. awake ECMO, ultraprotective ventilation, etc)
- Conditions
- Acute Respiratory Distress Syndrome, Barotrauma
- Being tested
- Blood and bronchoalveolar fluid collection and analysis, Chest CT scan
- Keywords
- Acute Respiratory Distress Syndrome, Mechanical Ventilation, Intensive Care, Respiratory Failure, Pneumothorax, Macklin effect
- Medical subject headings
- Respiratory Distress Syndrome, Barotrauma, Respiratory Insufficiency, Pneumothorax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood and bronchoalveolar fluid collection and analysisDiagnostic test
Blood and bronchoalveolar lavage fluid will be collected within 12 hours after intubation. Blood samples will be centrifuged, and the serum immediately stored at less than 70° C. The following biomarkers will be analysed in the serum and bronchoalveolar lavage fluid: 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-1(PAI-1), Receptor for Advanced Glycation Endproducts (RAGE), Intercellular adhesion molecule-1 (ICAM-1), Surfactant Protein D (SPD), protein C, Von Willebrand Factor (VWF), CXCL10/CXCR3, and metalloproteases (MMP9, MMP10). Blood samples obtained from the patients will be placed in specimen tubes containing heparin, centrifuged at 1500 G for 10 minutes, and then the plasma will be aspirated and stored at -70° C. Bronchoalveolar lavage fluid will be centrifuged at 1500 G for 10 minutes to remove cellular contents and stored at -70° C.
Chest CT scanDiagnostic test
Computed Tomography Scan per normal clinical practice
| Study group | Role | What they receive |
|---|---|---|
| Acute Respiratory Distress Syndrome | Patients with ARDS requiring or not requiring invasive ventilation Receives: Diagnostic Test: Blood and bronchoalveolar fluid collection and analysis; Diagnostic Test: Chest CT scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of clinically relevant barotrauma
Barotrauma is diagnosed only in the case of clear radiological evidence (free air at chest X-ray and/or chest CT scan).
Rate of barotrauma will be compared between patients with an hyperinflammatory pattern as compared with control.
Measured: 30 days or until hospital discharge. Specifically, from date of basal CT scan until the date of first radiologically documented barotrauma
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2023
- Study start27 Nov 2023
- Primary completionApr 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università Vita-Salute San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Landoni, Università Vita-Salute San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06001645
- Sponsor's protocol ID
- PNRR-MAD-2022-12376
- Acronym
- PIE-ARDS
- Status last verified
- Aug 2025
- First submitted
- 31 Jul 2023
- Last updated
- 12 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Murayama S, Gibo S. Spontaneous pneumomediastinum and Macklin effect: Overview and appearance on computed tomography. World J Radiol. 2014 Nov 28;6(11):850-4. doi: 10.4329/wjr.v6.i11.850.
PubMed 25431639Palumbo D, Zangrillo A, Belletti A, Guazzarotti G, Calvi MR, Guzzo F, Pennella R, Monti G, Gritti C, Marmiere M, Rocchi M, Colombo S, Valsecchi D, Scandroglio AM, Dagna L, Rovere-Querini P, Tresoldi M, Landoni G, De Cobelli F; COVID-BioB Study Group. A radiological predictor for pneumomediastinum/pneumothorax in COVID-19 ARDS patients. J Crit Care. 2021 Dec;66:14-19. doi: 10.1016/j.jcrc.2021.07.022. Epub 2021 Aug 12.
PubMed 34392131Belletti A, Pallanch O, Bonizzoni MA, Guidi L, De Cobelli F, Landoni G, Zangrillo A, De Bonis M, Palumbo D. Clinical use of Macklin-like radiological sign (Macklin effect): A systematic review. Respir Med. 2023 Apr-May;210:107178. doi: 10.1016/j.rmed.2023.107178. Epub 2023 Feb 28.
PubMed 36863617Paternoster G, Bertini P, Belletti A, Landoni G, Gallotta S, Palumbo D, Isirdi A, Guarracino F. Venovenous Extracorporeal Membrane Oxygenation in Awake Non-Intubated Patients With COVID-19 ARDS at High Risk for Barotrauma. J Cardiothorac Vasc Anesth. 2022 Aug;36(8 Pt B):2975-2982. doi: 10.1053/j.jvca.2022.03.011. Epub 2022 Mar 17.
PubMed 35537972Maccarrone V, Liou C, D'souza B, Salvatore MM, Leb J, Belletti A, Palumbo D, Landoni G, Capaccione KM. The Macklin effect closely correlates with pneumomediastinum in acutely ill intubated patients with COVID-19 infection. Clin Imaging. 2023 May;97:50-54. doi: 10.1016/j.clinimag.2023.03.003. Epub 2023 Mar 4.
PubMed 36889115Guarracino F, Baldassarri R, Brizzi G, Isirdi A, Landoni G, Marmiere M, Belletti A. Awake Venovenous Extracorporeal Membrane Oxygenation in the Intensive Care Unit: Challenges and Emerging Concepts. J Cardiothorac Vasc Anesth. 2025 Apr;39(4):1004-1014. doi: 10.1053/j.jvca.2024.12.045. Epub 2025 Jan 9.
PubMed 39843275Belletti A, D'Andria Ursoleo J, Piazza E, Mongardini E, Paternoster G, Guarracino F, Palumbo D, Monti G, Marmiere M, Calabro MG, Landoni G, Zangrillo A. Extracorporeal membrane oxygenation for prevention of barotrauma in patients with respiratory failure: A scoping review. Artif Organs. 2025 Feb;49(2):183-195. doi: 10.1111/aor.14864. Epub 2024 Sep 21.
PubMed 39305092
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulmonary Interstitial Emphysema (Macklin Effect), Quantitative Imaging Analysis and CytoKine Profiling to Predict Lung Frailty IN ARDS
- ClinicalTrials.gov ID
- NCT06001645
- Acronym / sponsor ID
- PIE-ARDS / PNRR-MAD-2022-12376
- Conditions
- Acute Respiratory Distress Syndrome, Barotrauma
- Keywords
- Acute Respiratory Distress Syndrome, Mechanical Ventilation, Intensive Care, Respiratory Failure, Pneumothorax, Macklin effect
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Università Vita-Salute San RaffaeleUniversity, hospital or other
- Study start
- 27 Nov 2023 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 21 Aug 2023 (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.
Barotrauma (pneumothorax, pneumomediastinum) is a well-described complication of Acute Respiratory Distress Syndrome (ARDS), especially in patients with coronavirus disease 2019 (COVID-19) (16.1% 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
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 (i.e. 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 (i.e. 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 airways/esophaegal 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: 89.2%; specificity: 95.6%). In our cohort, radiologically-detected Macklin effect was identified 8-12 days before development of pneumomediastinum/pneumothorax. These preliminary results have been confirmed in a subsequent multicenter study (sample size 697 patients; sensitivity: 100%; specificity: 99.8%).
Furthermore, preliminary data suggest that early application of awake veno/venous 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 CXCL10/CXCR3 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 retrospective/prospective 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-1(PAI-1), Receptor for Advanced Glycation Endproducts (RAGE), Intercellular adhesion molecule-1 (ICAM-1), Surfactant Protein D (SPD), protein C, Von Willebrand Factor (VWF), CXCL10/CXCR3, 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 (e.g. awake ECMO, ultraprotective ventilation, etc)
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acute Respiratory Distress Syndrome | – | Diagnostic Test: Blood and bronchoalveolar fluid collection and analysis, Diagnostic Test: Chest CT scanPatients with ARDS requiring or not requiring invasive ventilation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with ARDS diagnosis will be enrolled. With the exception of blood and BAL samples collection, all patients enrolled in the prospective cohort will follow their normal course of diagnosis/treatment without any further requirements for the scope of this study other than those provided in the normal management of patients with this condition. Furthermore, any decision regarding drug or procedure will be made by the physician based on her/his clinical judgment, independently from the decision to include the patient in this study. No follow-up medical and/or imaging examinations/laboratory analysis after hospital discharge are needed by the present study design.
Key inclusion criteria (3 listed)
- Clinical and radiological signs of ARDS, according to Berlin criteria, requiring ICU admission;
- Obtain duly signed informed consent
- Availability of at least one chest CT scan during hospital stay
Key exclusion criteria (1 listed)
- Poor quality imaging (because of motion/respiratory artefacts).
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 |
|---|---|---|
| Blood and bronchoalveolar fluid collection and analysisBlood and bronchoalveolar lavage fluid will be collected within 12 hours after intubation. Blood samples will be centrifuged, and the serum immediately stored at less than 70° C. The following biomarkers will be analysed in the serum and bronchoalveolar lavage fluid: 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-1(PAI-1), Receptor for Advanced Glycation Endproducts (RAGE), Intercellular adhesion molecule-1 (ICAM-1), Surfactant Protein D (SPD), protein C, Von Willebrand Factor (VWF), CXCL10/CXCR3, and metalloproteases (MMP9, MMP10). Blood samples obtained from the patients will be placed in specimen tubes containing heparin, centrifuged at 1500 G for 10 minutes, and then the plasma will be aspirated and stored at -70° C. Bronchoalveolar lavage fluid will be centrifuged at 1500 G for 10 minutes to remove cellular contents and stored at -70° C. | Diagnostic test | Acute Respiratory Distress Syndrome |
| Chest CT scanComputed Tomography Scan per normal clinical practice | Diagnostic test | Acute Respiratory Distress Syndrome |
Primary outcome
Rate of clinically relevant barotrauma
Time frame: 30 days or until hospital discharge. Specifically, from date of basal CT scan until the date of first radiologically documented barotrauma
Barotrauma is diagnosed only in the case of clear radiological evidence (free air at chest X-ray and/or chest CT scan). Rate of barotrauma will be compared between patients with an hyperinflammatory pattern as compared with control.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Background: PubMed 25431639Murayama S, Gibo S. Spontaneous pneumomediastinum and Macklin effect: Overview and appearance on computed tomography. World J Radiol. 2014 Nov 28;6(11):850-4. doi: 10.4329/wjr.v6.i11.850.
- Background: PubMed 34392131Palumbo D, Zangrillo A, Belletti A, Guazzarotti G, Calvi MR, Guzzo F, Pennella R, Monti G, Gritti C, Marmiere M, Rocchi M, Colombo S, Valsecchi D, Scandroglio AM, Dagna L, Rovere-Querini P, Tresoldi M, Landoni G, De Cobelli F; COVID-BioB Study Group. A radiological predictor for pneumomediastinum/pneumothorax in COVID-19 ARDS patients. J Crit Care. 2021 Dec;66:14-19. doi: 10.1016/j.jcrc.2021.07.022. Epub 2021 Aug 12.
- Background: PubMed 36863617Belletti A, Pallanch O, Bonizzoni MA, Guidi L, De Cobelli F, Landoni G, Zangrillo A, De Bonis M, Palumbo D. Clinical use of Macklin-like radiological sign (Macklin effect): A systematic review. Respir Med. 2023 Apr-May;210:107178. doi: 10.1016/j.rmed.2023.107178. Epub 2023 Feb 28.
- Background: PubMed 35537972Paternoster G, Bertini P, Belletti A, Landoni G, Gallotta S, Palumbo D, Isirdi A, Guarracino F. Venovenous Extracorporeal Membrane Oxygenation in Awake Non-Intubated Patients With COVID-19 ARDS at High Risk for Barotrauma. J Cardiothorac Vasc Anesth. 2022 Aug;36(8 Pt B):2975-2982. doi: 10.1053/j.jvca.2022.03.011. Epub 2022 Mar 17.
- Background: PubMed 36889115Maccarrone V, Liou C, D'souza B, Salvatore MM, Leb J, Belletti A, Palumbo D, Landoni G, Capaccione KM. The Macklin effect closely correlates with pneumomediastinum in acutely ill intubated patients with COVID-19 infection. Clin Imaging. 2023 May;97:50-54. doi: 10.1016/j.clinimag.2023.03.003. Epub 2023 Mar 4.
- Background: PubMed 39843275Guarracino F, Baldassarri R, Brizzi G, Isirdi A, Landoni G, Marmiere M, Belletti A. Awake Venovenous Extracorporeal Membrane Oxygenation in the Intensive Care Unit: Challenges and Emerging Concepts. J Cardiothorac Vasc Anesth. 2025 Apr;39(4):1004-1014. doi: 10.1053/j.jvca.2024.12.045. Epub 2025 Jan 9.
- Background: PubMed 39305092Belletti A, D'Andria Ursoleo J, Piazza E, Mongardini E, Paternoster G, Guarracino F, Palumbo D, Monti G, Marmiere M, Calabro MG, Landoni G, Zangrillo A. Extracorporeal membrane oxygenation for prevention of barotrauma in patients with respiratory failure: A scoping review. Artif Organs. 2025 Feb;49(2):183-195. doi: 10.1111/aor.14864. Epub 2024 Sep 21.
- Individual participant dataSharing planned: No
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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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Respiratory Distress Syndrome and Barotrauma, run by Università Vita-Salute San Raffaele at 4 sites in Italy.
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 1 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: looking for participants now, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of clinically relevant barotrauma (time frame: 30 days or until hospital discharge. Specifically, from date of basal CT scan until the date of first radiologically documented barotrauma). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06001645, which also lists 7 linked publications.
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 12 Aug 2025.