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

Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05492344
Collaborator
(none)
538
2
39

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: Personalized ventilation
  • Other: Standard care
N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
538 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Supportive Care
Official Title:
Personalized Mechanical Ventilation Guided by UltraSound in Patients With Acute Respiratory Distress Syndrome
Anticipated Study Start Date :
Aug 1, 2022
Anticipated Primary Completion Date :
Nov 1, 2025
Anticipated Study Completion Date :
Nov 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

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

Active Comparator: Standard care

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

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

Outcome Measures

Primary Outcome Measures

  1. All-cause mortality [90 days after inclusion]

    Any death during ICU- or hospital-stay at day 90

Secondary Outcome Measures

  1. All-cause mortality [28 days after inclusion]

    Any death during ICU- or hospital-stay at day 28

  2. Ventilator free days [28 days after inclusion]

    Duration of ventilation in survivors

  3. ICU length of stay [90 days after inclusion]

    Length of stay in the intensive care unit

  4. ICU mortality [90 days after inclusion]

    Mortality in the ICU

  5. Hospital length of stay [90 days after inclusion]

    Length of stay in the hospital

  6. Hospital mortality [90 days after inclusion]

    Mortality in the hospital

  7. Number of patients with Complications [90 days after inclusion]

    Ventilator associated pneumonia and pneumothorax

  8. Number of patients with Adjunctive therapies [90 days after inclusion]

    Extracorporeal membrane oxygenation (ECMO), recruitment, prone position

  9. Number of patients with Rescue therapies [90 days after inclusion]

    Inhaled vasodilators, airway pressure release ventilation

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 100 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

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

Investigators

  • Principal Investigator: Lieuwe DJ Bos, Dr., Amsterdam UMC, location AMC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Prof. Dr. Marcus J. Schultz, Principal Investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT05492344
Other Study ID Numbers:
  • PEGASUS
First Posted:
Aug 8, 2022
Last Update Posted:
Aug 8, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 8, 2022