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

NCT ID: NCT05492344

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 538 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-09
• Study Completion Date: 2027-11-01

Brief Summary

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.

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.

Conditions

ARDS, Human; Lung Ultrasound; Mechanical Ventilation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Personalized ventilation

Intervention Type: OTHER

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

Standard care

Patients assigned to the control group will be ventilated according to the current standard of care.

Group Type: ACTIVE_COMPARATOR

Standard care

Intervention Type: OTHER

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

Interventions

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

Intervention Type: 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

Intervention Type: OTHER

Eligibility Criteria

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 are moribund or facing end of life and
• no informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Marcus J. Schultz

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lieuwe DJ Bos, Dr.

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location AMC

Locations

Chu-Brugmann

Brussels, , Belgium

Site Status: RECRUITING

Bispebjerg Hospital

Copenhagen, , Denmark

Site Status: RECRUITING

Nordsjaellands Hospital

Hillerød, , Denmark

Site Status: RECRUITING

Evaggelismos Hospital

Athens, , Greece

Site Status: RECRUITING

Galway University Hospitals

Galway, , Ireland

Site Status: RECRUITING

Ospedale Generale Regionale F. Miulli

Acquaviva delle Fonti, Bari, Italy

Site Status: RECRUITING

Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari

Bari, , Italy

Site Status: RECRUITING

Amsterdam UMC, location VUmc

Amsterdam, North Holland, Netherlands

Site Status: RECRUITING

Amsterdam UMC, location AMC

Amsterdam, North Holland, Netherlands

Site Status: RECRUITING

Centralny Szpital Kliniczny MSWiA

Warsaw, , Poland

Site Status: RECRUITING

Countries

Belgium; Denmark; Greece; Ireland; Italy; Netherlands; Poland

Central Contacts

Jante S Sinnige, M.D.

Role: CONTACT

j.s.sinnige@amsterdamumc.nl

+31637405311

Marry R Smit, Dr.

Role: CONTACT

m.r.smit@amsterdamumc.nl

+3120 5666339

Facility Contacts

Charalampos Pierrakos, Dr.

Role: primary

Theis Skovsgaard Itenov, Dr.

Role: primary

Lars Hein, Drs.

Role: primary

Eleni Ischaki, Dr.

Role: primary

John Laffey, Prof.

Role: primary

Marco Pezzuto, Drs.

Role: primary

Claudio Zimatore, Drs.

Role: primary

Pieter Roel Tuinman, Dr.

Role: primary

Jante Sinnige, MD

Role: primary

j.s.sinnige@amsterdamumc.nl

Konstanty Szuldrzynski, Prof.

Role: primary

References

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.

Reference Type: DERIVED

PMID: 38715118 (View on PubMed)

Other Identifiers

PEGASUS

Identifier Type: -

Identifier Source: org_study_id