Personalized Mechanical Ventilation Guided by UltraSound in Patients With Acute Respiratory Distress Syndrome

Rationale Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. The identification of ARDS phenotypes, based on focal or non-focal lung morphology, can be helpful to better target mechanical ventilation strategies of individual patients. Lung ultrasound (LUS) is a non-invasive tool that can accurately distinguish 'focal' from 'non-focal' lung morphology. The investigators hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients will lead to a reduction in 90-day mortality compared to conventional mechanical ventilation.

Study Overview

• Status: Recruiting
• Conditions: ARDS, Human; Mechanical Ventilation; Lung Ultrasound
• Intervention / Treatment: Other: Personalized ventilation; Other: Standard care

Detailed Description

Objective The aim of this study is to determine if personalized mechanical ventilation based on lung morphology assessed by LUS leads to a reduced mortality compared to conventional mechanical ventilation in ARDS patients.

Study design The PEGASUS study is an investigator-initiated multicenter randomized clinical trial (RCT) with a predefined feasibility and safety evaluation after a pilot phase.

Study population This study will include 538 consecutively admitted invasively ventilated adult intensive care unit (ICU) patients with moderate or severe ARDS. There will be a predefined feasibility and safety evaluation after inclusion of the first 80 patients.

Intervention Patients will receive a LUS exam within 12 hours after diagnosis of ARDS to classify lung morphology as focal or non-focal ARDS. Immediately after the LUS exam patients will be randomly assigned to the intervention group, with personalized mechanical ventilation, or the control group, in which patients will receive standard care.

Main study parameters/endpoints The primary endpoint is all cause mortality at day 90 (diagnosis of ARDS considered as day 0). Secondary outcomes are mortality at 28 days, ventilator free days (VFD) at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality and number of complications (VAP, pneumothorax and need for rescue therapy). After a pilot phase, feasibility of LUS, correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation is evaluated to inform a stop-go decision.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness Patient burden and risks are low as the ventilation methods in this study are already commonly used in ICU practice; the collection of general data from hospital charts and (electronic) medical records systems causes no harm to the patients; LUS is not uncomfortable.

• Study Type: Interventional
• Enrollment (Estimated): 538
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jante S Sinnige, M.D.; Phone Number: +31637405311; Email: j.s.sinnige@amsterdamumc.nl
• Study Contact Backup: Name: Marry R Smit, Dr.; Phone Number: +3120 5666339; Email: m.r.smit@amsterdamumc.nl

Study Locations

• Belgium
  • Brussels, Belgium
    • Recruiting
    • Chu-Brugmann
    • Contact: Charalampos Pierrakos, Dr.
• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Bispebjerg Hospital
    • Contact: Theis Skovsgaard Itenov, Dr.
  • Hillerød, Denmark
    • Recruiting
    • Nordsjaellands Hospital
    • Contact: Lars Hein, Drs.
• Greece
  • Athens, Greece
    • Recruiting
    • Evaggelismos Hospital
    • Contact: Eleni Ischaki, Dr.
• Ireland
  • Galway, Ireland
    • Recruiting
    • Galway University Hospitals
    • Contact: John Laffey, Prof.
• Italy
  • Bari, Italy
    • Recruiting
    • Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
    • Contact: Claudio Zimatore, Drs.
  • Bari
    • Acquaviva delle Fonti, Bari, Italy
      • Recruiting
      • Ospedale Generale Regionale F. Miulli
      • Contact: Marco Pezzuto, Drs.
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081HV
      • Recruiting
      • Amsterdam UMC, location VUmc
      • Contact: Pieter Roel Tuinman, Dr.
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Recruiting
      • Amsterdam UMC, location AMC
      • Contact: Jante Sinnige, MD; Email: j.s.sinnige@amsterdamumc.nl
• Poland
  • Warsaw, Poland
    • Recruiting
    • Centralny Szpital Kliniczny Mswia
    • Contact: Konstanty Szuldrzynski, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Admitted to a participating ICU,
• invasively ventilated and
• fulfil the Berlin criteria for moderate or severe ARDS.

Exclusion Criteria:

• Age under 18,
• participation in other interventional studies with conflicting endpoints,
• conditions in which LUS is not feasible or possible (e.g. subcutaneous emphysema, morbid obesity or wounds),
• mechanical ventilation for longer than 7 consecutive days in the past 30 days,
• history of ARDS in the previous month,
• body-mass index higher than 40 kg/m²,
• intracranial hypertension,
• broncho-pleural fistula,
• chronic respiratory diseases requiring long-term oxygen therapy or respiratory support,
• pulmonary fibrosis with a vital capacity < 50% (severe or very severe),
• previously randomized in the PEGASUS study
• ECMO
• patients who receive invasive ventilation in home setting due to a neurological disease
• pregnant patients
• patients who are moribund or facing end of life and
• no informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalized ventilation; If a patient is assigned to the intervention group, ventilator settings will be adjusted based on the lung morphology (focal or non focal) results of the lung ultrasound.	Other: Personalized ventilation; Patients who are randomized for personalized ventilation with FOCAL ARDS will receive the following ventilator settings: Positive end-expiratory pressure (PEEP) ≤ 9 cm water (H2O); Tidal volume: 6 to 8 mL/kg predicted body weight (PBW); Daily prone positioning LUS will be repeated every 48-72 hours in supine position for the focal ARDS patients to assess whether they have developed non-focal ARDS during admission. In that case, patients will from then on be treated according non-focal personalized treatment protocol. Patients who are randomized for personalized ventilation with Non-FOCAL ARDS will receive the following ventilator settings: PEEP ≥ 15 cm H2O; Tidal volume: 4 to 6 mL/kg PBW; Daily recruitment maneuver
Active Comparator: Standard care; Patients assigned to the control group will be ventilated according to the current standard of care.	Other: Standard care; Patient who are randomized in the control group will receive standard care; Tidal volume: 6 mL/kg PBW; PEEP and FiO2 according to the low PEEP and high fraction of inspired oxygen (FiO2) table of the AlVEOLI study; Prone positioning if the Partial Pressure of Oxygen (PaO2) /FiO2 ratio is < 150 mmHg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Any death during ICU- or hospital-stay at day 90	90 days after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Any death during ICU- or hospital-stay at day 28	28 days after inclusion
Ventilator free days	Duration of ventilation in survivors	28 days after inclusion
ICU length of stay	Length of stay in the intensive care unit	90 days after inclusion
ICU mortality	Mortality in the ICU	90 days after inclusion
Hospital length of stay	Length of stay in the hospital	90 days after inclusion
Hospital mortality	Mortality in the hospital	90 days after inclusion
Number of patients with Complications	Ventilator associated pneumonia and pneumothorax	90 days after inclusion
Number of patients with Adjunctive therapies	Extracorporeal membrane oxygenation (ECMO), recruitment, prone position	90 days after inclusion
Number of patients with Rescue therapies	Inhaled vasodilators, airway pressure release ventilation	90 days after inclusion

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Lieuwe DJ Bos, Dr., Amsterdam UMC, location AMC

Publications and helpful links

General Publications

• Sinnige JS, Smit MR, Ghose A, de Grooth HJ, Itenov TS, Ischaki E, Laffey J, Paulus F, Povoa P, Pierrakos C, Pisani L, Roca O, Schultz MJ, Szuldrzynski K, Tuinman PR, Zimatore C, Bos LDJ; PEGASUS investigators. Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial. Trials. 2024 May 7;25(1):308. doi: 10.1186/s13063-024-08140-7.
• Sinnige JS, Smit MR, Alam MJ, Chowdhury MNH, Costa V, de Castro HSMB, Daszuta D, Filippini DFL, Ghose A, de Grooth HJ, Hein L, Hermans G, Hildebrandt T, Itenov TS, Ischaki E, Klompmaker P, Laffey J, McMahon A, McNicholas B, Mousa A, Paulus F, Pedersen UG, Pellegrini M, Pezzuto M, Povoa P, Pierrakos C, Pisani L, Roca O, Schultz MJ, Spadaro S, Szuldrzynski K, Theodorou E, Tuinman PR, Wamberg CA, Zimatore C, Bos LDJ; PEGASUS investigators. Personalized mechanical ventilation guided by lung ultrasound in patients with ARDS: a pilot phase of a randomized clinical trial. Intensive Care Med Exp. 2025 Dec 22;13(1):135. doi: 10.1186/s40635-025-00835-8.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: PEGASUS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No