Clinical trial NCT05492344: Personalized Mechanical Ventilation Guided by UltraSound in Patients With Acute Respiratory Distress Syndrome
Official title: Personalized Mechanical Ventilation Guided by UltraSound in Patients With Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ARDS, Human
Lung Ultrasound
Mechanical Ventilation
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2022-08-08
Enrollment: 538
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: All-cause mortality
timeFrame: 90 days after inclusion
Secondary outcomes:
measure: All-cause mortality
timeFrame: 28 days after inclusion
measure: Ventilator free days
timeFrame: 28 days after inclusion
measure: ICU length of stay
timeFrame: 90 days after inclusion
measure: ICU mortality
timeFrame: 90 days after inclusion
measure: Hospital length of stay
timeFrame: 90 days after inclusion
measure: Hospital mortality
timeFrame: 90 days after inclusion
measure: Number of patients with Complications
timeFrame: 90 days after inclusion
measure: Number of patients with Adjunctive therapies
timeFrame: 90 days after inclusion
measure: Number of patients with Rescue therapies
timeFrame: 90 days after inclusion
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Chu-Brugmann
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Hillerød
country: Denmark
facility: Nordsjaellands Hospital
city: Athens
country: Greece
facility: Evaggelismos Hospital
city: Galway
country: Ireland
facility: Galway University Hospitals
city: Acquaviva Delle Fonti
country: Italy
facility: Ospedale Generale Regionale F. Miulli
state: Bari
city: Bari
country: Italy
facility: Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUmc
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
state: Noord-Holland
city: Warsaw
country: Poland
facility: Centralny Szpital Kliniczny MSWiA
Study officials:
affiliation: Amsterdam UMC, location AMC
name: Lieuwe DJ Bos, Dr.
role: PRINCIPAL_INVESTIGATOR
References: