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

Mechanical Ventilation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05492344
• Other study ID #: PEGASUS
• Status: Recruiting
• Phase: N/A
• Start date: August 9, 2022
• Est. completion date: November 1, 2026

Study information

• Verified date: January 2024
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Jante S Sinnige, M.D.
• Phone: +31637405311
• Email: j.s.sinnige[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 538
• Est. completion date: November 1, 2026
• Est. primary completion date: August 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• ARDS, Human
• Lung Ultrasound
• Mechanical Ventilation
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

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
• 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

Locations

Country	Name	City	State
Belgium	Chu-Brugmann	Bruxelles
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Nordsjaellands Hospital	Hillerød
Greece	Evaggelismos Hospital	Athens
Ireland	Galway University Hospitals	Galway
Italy	Ospedale Generale Regionale F. Miulli	Acquaviva Delle Fonti	Bari
Italy	Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari	Bari
Netherlands	Amsterdam UMC, location AMC	Amsterdam	Noord-Holland
Netherlands	Amsterdam UMC, location VUmc	Amsterdam	Noord-Holland
Poland	Centralny Szpital Kliniczny MSWiA	Warsaw

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Countries where clinical trial is conducted

Belgium,  Denmark,  Greece,  Ireland,  Italy,  Netherlands,  Poland, 

Outcome

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