Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial.

Humans Respiratory Distress Syndrome / therapy Respiration, Artificial / methods Randomized Controlled Trials as Topic Lung / diagnostic imaging Treatment Outcome Ultrasonography, Interventional / methods Time Factors Multicenter Studies as Topic Predictive Value of Tests Precision Medicine / methods
Acute respiratory distress syndrome Lung ultrasound Mechanical ventilation Personalized medicine

Journal

Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253

Informations de publication

Date de publication:
07 May 2024
Historique:
received: 22 12 2023
accepted: 26 04 2024
medline: 8 5 2024
pubmed: 8 5 2024
entrez: 7 5 2024
Statut: epublish

Résumé

Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

Sections du résumé

BACKGROUND BACKGROUND
Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation.
METHODS METHODS
The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated.
DISCUSSION CONCLUSIONS
PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach.
TRIAL REGISTRATION BACKGROUND
The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

Identifiants

DOI: 10.1186/s13063-024-08140-7 PMID: 38715118
pubmed: 38715118
doi: 10.1186/s13063-024-08140-7
pii: 10.1186/s13063-024-08140-7
doi:

Banques de données

ClinicalTrials.gov
['NCT05492344']

Types de publication

Clinical Trial Protocol Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

308

Investigateurs

A K M Arif Uddin Ahmed (AKMAU)
Mohammad Jhahidul Alam (MJ)
Mohsammad Rafiqual Alam (MR)
Anjan Bal (A)
Samarjit Barua (S)
Rajdeep Biswas (R)
Mohammed Abdur Rahaman Chowdhury (MAR)
Safiqul Mostafa Chy (SM)
Satyajit Dhar (S)
Pranay Kumar Dutta (PK)
Syeda Nafisa Khatoon (SN)
Ranjan Kumar Nath (RK)
Nahid Nowroz (N)
Mithun Shil (M)
Rachid Attou (R)
Leonel Barreto Gutierrez (LB)
Keitiane Kaefer (K)
Morten Bestle (M)
Lars Hein (L)
Thomas Hildebrandt (T)
Jacob Jensen (J)
Sanne Lauritzen (S)
Ulf Pedersen (U)
Lone Poulsen (L)
Harry Giannopoulos (H)
Katerina Vaporidi (K)
Lauren Ferguson (L)
Yvelynne Kelly (Y)
Sabina Mason (S)
Aisling McMahon (A)
Bairbre McNicholas (B)
Daniele Biasucci (D)
Gianmaria Cammarota (G)
Maurizio Follino (M)
Salvatore Grasso (S)
Antonio Latela (A)
Giovanna Magnesa (G)
Fabrizia Massaro (F)
Leonarda Maurmo (L)
Marco Pezzuto (M)
Savino Spadaro (S)
Luigi Vetrugno (L)
Massimo Zambon (M)
Daan Filippini (D)
Peter Klompmaker (P)
Amne Mousa (A)
Dominik Daszuta (D)
Miłosz Jankowski (M)
Irene Aragao (I)
Heloisa Castro (H)
Vasco Costa (V)
Cristina Torrão (C)
Toni Antoni (T)
Marta Arroyo (M)
Marta Briva (M)
Nuria Duran (N)
Marina García-de-Acilu (M)
Gemma Goma (G)
Ana Ochagavia (A)
Michelle Chew (M)
Mariangela Pellegrini (M)
Gaetano Perchiazzi (G)

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Jante S Sinnige (JS)

Department of Intensive Care, Amsterdam University Medical Centres (UMC), University of Amsterdam, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands. j.s.sinnige@amsterdamumc.nl.
ORCID: 0000-0002-8906-0071

Marry R Smit (MR)

Department of Intensive Care, Amsterdam University Medical Centres (UMC), University of Amsterdam, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands.

Aniruddha Ghose (A)

Department of Medicine, Chattogram Medical Centre, Chattogram, Bangladesh.

Harm-Jan de Grooth (HJ)

Department of Intensive Care, UMC, Vrije Universiteit, Amsterdam, HV, 1081, The Netherlands.

Theis Skovsgaard Itenov (TS)

Department of Anesthesiology and Intensive Care, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Eleni Ischaki (E)

First Department of Intensive Care Medicine, University of Athens Medical School, 10676, Athens, AZ, Greece.

John Laffey (J)

Anaesthesia and Intensive Care Medicine, School of Medicine, Galway University Hospitals, University of Galway, Galway, H91 TK33, Ireland.

Frederique Paulus (F)

Department of Intensive Care, Amsterdam University Medical Centres (UMC), University of Amsterdam, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands.

Pedro Póvoa (P)

NOVA Medical School, CHRC, NOVA University of Lisbon, Lisbon, Portugal.
Center for Clinical Epidemiology and Research Unit of Clinical Epidemiology, OUH Odense University Hospital, Odense, Denmark.
Department of Intensive Care, Hospital de São Francisco Xavier, CHLO, Lisbon, Portugal.

Charalampos Pierrakos (C)

Department of Intensive Care, Amsterdam University Medical Centres (UMC), University of Amsterdam, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands.
Department of Intensive Care, Brugmann University Hospital, Université Libre de Bruxelles, 1050, Brussels, Belgium.

Luigi Pisani (L)

Department of Intensive Care, Amsterdam University Medical Centres (UMC), University of Amsterdam, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands.
Department of Precision-Regenerative Medicine and Jonic Area (DiMePRe-J), Section of Anesthesiology and Intensive Care Medicine, University of Bari Aldo Moro, Bari, Italy.

Oriol Roca (O)

Servei de Medicina Intensiva, Parc Taulí Hospital Universitari, Institut de Recerca Part Taulí (I3PT-CERCA), Parc del Taulí 1, 08028, Sabadell, Spain.
Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.

Marcus J Schultz (MJ)

Department of Intensive Care, Amsterdam University Medical Centres (UMC), University of Amsterdam, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands.
Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, 10400, Thailand.
Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.

Konstanty Szuldrzynski (K)

Department of Anaesthesiology and Intensive Care, National Institute of Medicine of the Ministry of Interior and Administration, 02-507, Warsaw, Poland.

Pieter R Tuinman (PR)

Department of Intensive Care, UMC, Vrije Universiteit, Amsterdam, HV, 1081, The Netherlands.
Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, Netherlands.

Claudio Zimatore (C)

Department of Intensive Care, Amsterdam University Medical Centres (UMC), University of Amsterdam, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands.
Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, 70124, Bari, Italy.

Lieuwe D J Bos (LDJ)

Department of Intensive Care, Amsterdam University Medical Centres (UMC), University of Amsterdam, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands.
Department of Pulmonology, Amsterdam UMC, University of Amsterdam, Amsterdam, AZ, 1105, The Netherlands.
Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam, AZ, 1105, The Netherlands.

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