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

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).

• Authors: Jante S Sinnige, Marry R Smit, Aniruddha Ghose, Harm-Jan de Grooth, Theis Skovsgaard Itenov, Eleni Ischaki, John Laffey, Frederique Paulus, Pedro Póvoa, Charalampos Pierrakos, Luigi Pisani, Oriol Roca, Marcus J Schultz, Konstanty Szuldrzynski, Pieter R Tuinman, Claudio Zimatore, Lieuwe D J Bos, PEGASUS investigators
• Journal: Trials (Trials) Vol. 25 Issue 1 Pg. 308 (May 07 2024) ISSN: 1745-6215 [Electronic] England
• PMID: 38715118 (Publication Type: Clinical Trial Protocol, Journal Article)
• Copyright: © 2024. The Author(s).

Topics

• Humans
• Respiratory Distress Syndrome (therapy, diagnostic imaging, mortality)
• Respiration, Artificial (methods)
• Randomized Controlled Trials as Topic
• Lung (diagnostic imaging, physiopathology)
• Treatment Outcome
• Ultrasonography, Interventional (methods)
• Time Factors
• Multicenter Studies as Topic
• Predictive Value of Tests
• Precision Medicine (methods)