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).

Keywords: Acute respiratory distress syndrome; Lung ultrasound; Mechanical ventilation; Personalized medicine.

Fig. 1

This logarithm is used to determine the lung morphology by ultrasound of eligible patients. The scores are LUS aeration scores explained in supplement 1 based on a 12-region LUS exam. LUS lung ultrasound

Fig. 2

Flow diagram for enrollment of a PEGASUS participant. Patients with “focal” ARDS randomized in the intervention group will receive follow-up LUS exams to evaluate if their condition deteriorates to a “non-focal” ARDS. * ventilation strategy in Table 1. ARDS acute respiratory distress syndrome, LUS lung ultrasound

Fig. 3

Timeline for a study participant from enrollment until last day of follow-up. ^aIf a patient has “focal” ARDS and is randomized to personalized ventilation, a LUS will be repeated every 72 h. ^bInformed consent is obtained before randomization or deferred consent is obtained within 72 h after randomization depending on the local regulations. ^cUntil day 7 or until extubation. ^dUntil day 7 or ICU discharge. ^eUntil day 90 or ICU discharge. ^fUntil day 90 or hospital discharge. SOFA, Sequential Organ Failure Assessment; ICU, intensive care unit