Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial
Authors: Sinnige Jante S. , Smit Marry R. , Ghose Aniruddha , de Grooth Harm-Jan , Itenov Theis Skovsgaard , Ischaki Eleni , Laffey John , Paulus Frederique , Póvoa Pedro , Pierrakos Charalampos , Pisani Luigi , Roca Oriol , Schultz Marcus J. , Szuldrzynski Konstanty , Tuinman Pieter R. , Zimatore Claudio , Bos Lieuwe D. J. ,   for the PEGASUS investigators, Ahmed A. K. M. Arif Uddin , Alam Mohammad Jhahidul , Alam Mohsammad Rafiqual , Bal Anjan , Barua Samarjit , Biswas Rajdeep , Chowdhury Mohammed Abdur Rahaman , Chy Safiqul Mostafa , Dhar Satyajit , Dutta Pranay Kumar , Khatoon Syeda Nafisa , Nath Ranjan Kumar , Nowroz Nahid , Shil Mithun , Attou Rachid , Gutierrez Leonel Barreto , Kaefer Keitiane , Bestle Morten , Hein Lars , Hildebrandt Thomas , Jensen Jacob , Lauritzen Sanne , Pedersen Ulf , Poulsen Lone , Giannopoulos Harry , Vaporidi Katerina , Ferguson Lauren , Kelly Yvelynne , Mason Sabina , McMahon Aisling , McNicholas Bairbre , Biasucci Daniele , Cammarota Gianmaria , Follino Maurizio , Grasso Salvatore , Latela Antonio , Magnesa Giovanna , Massaro Fabrizia , Maurmo Leonarda , Pezzuto Marco , Spadaro Savino , Vetrugno Luigi , Zambon Massimo , Filippini Daan , Klompmaker Peter , Mousa Amne , Daszuta Dominik , Jankowski Miłosz , Aragao Irene , Castro Heloisa , Costa Vasco , Torrão Cristina , Antoni Toni , Arroyo Marta , Briva Marta , Duran Nuria , García-de-Acilu Marina , Goma Gemma , Ochagavia Ana , Chew Michelle , Pellegrini Mariangela , Perchiazzi Gaetano 
Published: May 2024

Abstract

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
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
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
The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).