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

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

Status: Enrolling

Conditions: Lung Ultrasound; ARDS, Human; Mechanical Ventilation

Treatments: Other: Standard care; Other: Personalized ventilation

Study type: Interventional

Funder types: Other

Identifiers

NCT05492344

PEGASUS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 538 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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538 participants in 2 patient groups

Personalized ventilation

Experimental group

Description:

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.

Treatment:

Other: Personalized ventilation

Standard care

Active Comparator group

Description:

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

Treatment:

Other: Standard care