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

Overview

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.

Interventions

• 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 pers
• 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

Primary outcome measures

• All-cause mortality [Time frame: 90 days after inclusion]

Secondary outcome measures (9)

• All-cause mortality [Time frame: 28 days after inclusion]
• Ventilator free days [Time frame: 28 days after inclusion]
• ICU length of stay [Time frame: 90 days after inclusion]
• ICU mortality [Time frame: 90 days after inclusion]
• Hospital length of stay [Time frame: 90 days after inclusion]
• Hospital mortality [Time frame: 90 days after inclusion]
• Number of patients with Complications [Time frame: 90 days after inclusion]
• Number of patients with Adjunctive therapies [Time frame: 90 days after inclusion]
• Number of patients with Rescue therapies [Time frame: 90 days after inclusion]

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 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

Denmark · 2 centers

• Bispebjerg Hospital — Copenhagen
• Nordsjaellands Hospital — Hillerød

Italy · 2 centers

• Ospedale Generale Regionale F. Miulli — Acquaviva delle Fonti
• Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari — Bari

Netherlands · 2 centers

• Amsterdam UMC, location VUmc — Amsterdam
• Amsterdam UMC, location AMC — Amsterdam

Belgium · 1 center

• Chu-Brugmann — Brussels

Greece · 1 center

• Evaggelismos Hospital — Athens

Ireland · 1 center

• Galway University Hospitals — Galway

Poland · 1 center

• Centralny Szpital Kliniczny MSWiA — Warsaw

Publications

• 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, Zim PMID 41423518
• 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 PMID 38715118

Identifiers

NCT: NCT05492344 · PEGASUS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗