Imaging Biomarkers to Stratify the Risk of Barotrauma in ARDS

NCT05816954 | Recruiting DMC

• 1 other identifier: FRAIL ARDS - 49/INT/2022
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

The high incidence of barotrauma in patients with COVID-19-related acute respiratory distress syndrome (ARDS) (16.1%, with a mortality rate \>60%) provides rationale for considering COVID-19 ARDS a paradigm for lung frailty. The investigators recently discovered that the Macklin effect is an impressive radiological predictor of barotrauma in COVID-19 ARDS. Since lung frailty is a major issue also in non-COVID-19 ARDS (6% barotrauma, with a mortality rate of 46% ) the investigators want to confirm the importance of Macklin effect in non-COVID-19 ARDS. Using artificial intelligence-based approaches the investigators also want to identify imaging biomarkers to non-invasively assess lung frailty in a mixed cohort of COVID-19/non-COVID-19 ARDS patients. Furthermore, the investigators want to prospectively validate these biomarkers in a cohort of ARDS patients. This will provide a therapeutic algorithm for ARDS patients at high-risk for barotrauma, identifying those most likely to benefit from hyper protective strategies.

Conditions

Acute Respiratory Distress Syndrome; Barotrauma

Outcome Measures

Primary Outcomes (1)

• 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). When a "central" (non-alveolar) cause of barotrauma (tracheal fissure, esophageal rupture) is suspected, endoscopy will be performed. Patients with barotrauma occurring within twelve hours from a chest interventional procedure (e.g. drains placement, central venous catheters insertion) will be excluded.

  30 days or until hospital discharge. Specifically, from date of basal CT scan until the date of first radiologically documented barotrauma.

Interventions

Chest Computed Tomography Scan per normal clinical practice DIAGNOSTIC_TEST

Normal Clinical practice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with ARDS clinical suspicion or diagnosis will be enrolled; specifically, these patients will be admitted at intensive care unit. 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 in the context of clinical practice, 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.

You may qualify if:

• Clinical and radiological signs of ARDS, according to Berlin criteria \[14\], requiring ICU admission;
• Obtain duly signed informed consent.

You may not qualify if:

• Poor quality imaging (because of motion/respiratory artefacts).

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead

Study Sites (2)

Ospedale Mater Domini

Catanzaro, Calabria, Italy

RECRUITING

IRCCS San Raffaele Scientific Institute

Milan, MI, 20132, Italy

RECRUITING

Related Publications (13)

• Belletti A, Todaro G, Valsecchi G, Losiggio R, Palumbo D, Landoni G, Zangrillo A. Barotrauma in Coronavirus Disease 2019 Patients Undergoing Invasive Mechanical Ventilation: A Systematic Literature Review. Crit Care Med. 2022 Mar 1;50(3):491-500. doi: 10.1097/CCM.0000000000005283.

  PMID: 34637421 BACKGROUND

• Palumbo D, Campochiaro C, Belletti A, Marinosci A, Dagna L, Zangrillo A, De Cobelli F; COVID-BioB Study Group. Pneumothorax/pneumomediastinum in non-intubated COVID-19 patients: Differences between first and second Italian pandemic wave. Eur J Intern Med. 2021 Jun;88:144-146. doi: 10.1016/j.ejim.2021.03.018. Epub 2021 Mar 19. No abstract available.

  PMID: 33820685 BACKGROUND

• Sakai M, Murayama S, Gibo M, Akamine T, Nagata O. Frequent cause of the Macklin effect in spontaneous pneumomediastinum: demonstration by multidetector-row computed tomography. J Comput Assist Tomogr. 2006 Jan-Feb;30(1):92-4. doi: 10.1097/01.rct.0000187416.07698.8d.

  PMID: 16365580 BACKGROUND

• 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.

  PMID: 25431639 BACKGROUND

• Russell DW, Watts JR Jr, Powers TA. Searching for the Source of the Leak: PIE and the Macklin Effect. Ann Am Thorac Soc. 2018 Nov;15(11):1354-1356. doi: 10.1513/AnnalsATS.201803-200CC. No abstract available.

  PMID: 30382777 BACKGROUND

• Belletti A, Palumbo D, Zangrillo A, Fominskiy EV, Franchini S, Dell'Acqua A, Marinosci A, Monti G, Vitali G, Colombo S, Guazzarotti G, Lembo R, Maimeri N, Faustini C, Pennella R, Mushtaq J, Landoni G, Scandroglio AM, Dagna L, De Cobelli F; COVID-BioB Study Group. Predictors of Pneumothorax/Pneumomediastinum in Mechanically Ventilated COVID-19 Patients. J Cardiothorac Vasc Anesth. 2021 Dec;35(12):3642-3651. doi: 10.1053/j.jvca.2021.02.008. Epub 2021 Feb 6.

  PMID: 33678544 BACKGROUND

• Palumbo 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.

  PMID: 34392131 BACKGROUND

• Paternoster G, Belmonte G, Scarano E, Rotondo P, Palumbo D, Belletti A, Corradi F, Bertini P, Landoni G, Guarracino F; COVID-Macklin Study Group. Macklin effect on baseline chest CT scan accurately predicts barotrauma in COVID-19 patients. Respir Med. 2022 Jun;197:106853. doi: 10.1016/j.rmed.2022.106853. Epub 2022 Apr 20.

  PMID: 35512457 BACKGROUND

• Paternoster 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.

  PMID: 35537972 BACKGROUND

• Mori M, Palumbo D, De Lorenzo R, Broggi S, Compagnone N, Guazzarotti G, Giorgio Esposito P, Mazzilli A, Steidler S, Pietro Vitali G, Del Vecchio A, Rovere Querini P, De Cobelli F, Fiorino C. Robust prediction of mortality of COVID-19 patients based on quantitative, operator-independent, lung CT densitometry. Phys Med. 2021 May;85:63-71. doi: 10.1016/j.ejmp.2021.04.022. Epub 2021 Apr 30.

  PMID: 33971530 BACKGROUND

• Mori M, Alborghetti L, Palumbo D, Broggi S, Raspanti D, Rovere Querini P, Del Vecchio A, De Cobelli F, Fiorino C. Atlas-based lung segmentation combined with automatic densitometry characterization in COVID-19 patients: Training, validation and first application in a longitudinal study. Phys Med. 2022 Aug;100:142-152. doi: 10.1016/j.ejmp.2022.06.018. Epub 2022 Jul 4.

  PMID: 35839667 BACKGROUND

• Palumbo D, Mori M, Prato F, Crippa S, Belfiori G, Reni M, Mushtaq J, Aleotti F, Guazzarotti G, Cao R, Steidler S, Tamburrino D, Spezi E, Del Vecchio A, Cascinu S, Falconi M, Fiorino C, De Cobelli F. Prediction of Early Distant Recurrence in Upfront Resectable Pancreatic Adenocarcinoma: A Multidisciplinary, Machine Learning-Based Approach. Cancers (Basel). 2021 Sep 30;13(19):4938. doi: 10.3390/cancers13194938.

  PMID: 34638421 BACKGROUND

• ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.

  PMID: 22797452 BACKGROUND

MeSH Terms

Conditions

Respiratory Distress Syndrome; Barotrauma

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Wounds and Injuries

Study Officials

• Giovanni Landoni, Professor

  Vita-Salute San Raffaele University

  STUDY CHAIR

Central Study Contacts

Diego Palumbo, MD

CONTACT

+39022643; palumbo.diego@hsr.it

Alessandro Belletti, MD

CONTACT

+39022643; belletti.alessandro@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Full Professor

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: April 18, 2023
• Study Start: August 30, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 6, 2025

Record last verified: 2025-08

Locations

IT (2)