PEGASUS study | ICU Research

News

6 januari 2023

Happy 2023!

Happy 2023 from the PEGASUS study team. We've started the new year with ethics approval in the Netherlands, Poland, Italy, Portugal, Denmark and Belgium! Early this year many centres in these countries will start patient inclusion. Based on the experience of the first 8 patients we included in Amsterdam, we are writing a detailed handbook on how to guide mechanical ventilation in PEGASUS patients.

28 oktober 2022

Co-investigator meeting for the PEGASUS study

The first PEGASUS co-investigator meeting has been planned for the 5th of December 2022.

17 oktober 2022

First patient in PEGASUS study

The first PEGASUS patient has been included in the Amsterdam UMC.

Currently recruiting centers

2 centers in the Netherlands, 2 centers in Italy, 2 centers in Denmark, 1 center in Belgium, 1 center in Ireland, 1 center in Greece, 1 center in Poland, 2 centers in Portugal, 1 center in Spain

76 patients included (April 2024)

Countries with ethics approval

Approval in: Netherlands, Italy, Poland, Portugal, Belgium, Bangladesh, Ireland, Spain and Denmark
Approval pending in: Sweden

Study 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. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients will lead to a reduction in 90-day mortality compared to conventional mechanical ventilation.

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 international, investigator-initiated multicenter randomized clinical trial (RCT).

Study population

This study will include 538 consecutively admitted invasively ventilated adult intensive care unit (ICU) patients with moderate or severe ARDS.

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. In the intervention group, patients with focal lung morphology will receive daily prone positioning with lower positive end-expiratory pressure (PEEP) and patients with non-focal lung morphology will receive daily recruitment maneuvers with higher PEEP.

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).

Documents

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Study team

Steering committee

Dr. Lieuwe D.J. Bos	Drs. Jante Sinnige
Dr. Harm-Jan de Grooth	Dr. Marry Smit
Prof. Dr. Frederique Paulus	Dr. Pieter-Roel Tuinman

Academic advisor

Prof. Dr. Marcus J. Schultz

Data and Safety Monitoring Board

Prof. Danny McAuley, Head of the DSMB

Royal Victoria Hospital and Queen's University of Belfast, Belfast, Ireland.

Dr. Dave Dongelmans

Amsterdam UMC, Amsterdam, the Netherlands

Dr. Rik Endeman

Erasmus MC, Rotterdam, the Netherlands

Dr. Ary Serpa Neto, independent statistician

Australian and New Zealand Intensive Care-Research Centre (ANZIC-RC), Melbourne, Australia

National Coordinators

Bangladesh: Prof. A. Faiz & Dr. L. Pisani	Italy: Dr. C. Zimatore
Belgium: Dr. C. Pierrakos	Portugal: Dr. P. Povoa
France: Prof. J-M. Constantin	Poland: Dr. K. Szułdrzyński
Czech Republic: Dr. Petr Waldauf	Denmark: Dr. T. Skovsgaard Itenov
Spain: Dr. O. Roca
Ireland: Prof. J. Laffey

eCRF

https://data.castoredc.com/

The eCRF is built in Castor EDC, a program that can be reached from everywhere via the internet. Randomization and reporting of protocol deviations will also be performed in this system.

Trial registration

https://clinicaltrials.gov/ct2/show/NCT05492344

Registration of the PEGASUS study at clinicaltrials.gov.

FAQ

Participate in PEGASUS

What are the criteria for co-authorship?

In the PEGASUS study, all rewards will be shared. There will be one co-author spot for each center that includes a patient. Each center will receive an additional co-author sport per 20 inclusions. The steering committee and international advisory committee (national coordinators), will also receive a co-author spot.

How is lung ultrasound training arranged?

Correct lung ultrasound assessment of lung morphology is crucial for the PEGASUS study. In each center, the local study coordinator will receive an E-learning with exam and will need to upload a case exam before enrolment can be started. A link to the E-learning can be provided to you by the PEGASUS study team. The PEGASUS study team will offer live lung ultrasound support for the first two inclusions and more if needed.

How many patients are expected to be included per center?

Around 40-50 centers will include patients for the PEGASUS study, resulting in around 10 inclusions per center.

How is the moment of diagnosis of ARDS defined?

ARDS is diagnosed by the treating physician. After the physician recognizes that a patients fulfils the Berlin criteria for moderate/severe ARDS, the patient needs to be randomized within 12 hours.

Can a patient be enrolled when he/she already participates in another RCT?

Yes, but only if the other RCT does not have mortality/duration of ventilation as primary outcome.

Is ECCO2R an exclusion criterion?

No, patients on ECCO2R can be included, but ECMO is an exclusion criterion.

Can ARDS patients in the personalized study arm switch morphology groups?

In patients with focal lung morphology in the personalized study arm, lung ultrasound will be repeated after 2-3 days to assess if a patient did not develop non-focal lung morphology. If a patient switched to non-focal lung morphology at the second ultrasound, personalized ventilation will be aligned with non-focal lung morphology.

Lung ultrasound will not be repeated in patients with non-focal lung morphology in the personalized arm as switching from non-focal to focal lung morphology is considered as a direct effect of the study intervention.

When will the personalized ventilation strategy be released?

Non-focal group:

If patients are breathing spontaneously, PEEP may be decreased from at least 15 cmH2O to 10 cmH2O.
PEEP may be reduced when the PaO2/FiO2 in supine position is > 200 mmHg and FiO2 is < 50%.

Focal group:

Prone positioning may be stopped when the PaO2/FiO2 in supine position is > 200 mmHg, FiO2 is < 50% and PEEP is 5 cmH2O.

Is adaptive ventilation allowed?

Yes, adaptive ventilation is allowed when the tidal volume and PEEP are set according to study protocol.

Are there guidelines on when to use rescue therapies, or when to deviate from the protocol?

Use of rescue therapies is up to the discretion of the treating physician. We recommend use of rescue therapies in the following situations:

Non-focal personalized group:

Prone positioning can be used as rescue therapy when the PaO2/FiO2 < 150 for 6 hours in supine position and FiO2 is already > 80%.
We also advice to lower the PEEP below 15 cmH2O when patients have a plateau pressure of 30 cmH2O during an inspiratory hold.

Focal personalized group:

PEEP can be increased > 9 cmH2O and recruitment can be used as a rescue therapy when the PaO2/FiO2 < 100 in prone position and FiO2 is already > 80%.

Which (serious) adverse events should be reported?

Occurrence of (serious) adverse events are captured within the eCRF in Castor. Events and complications that will be collected are: ventilator associated pneumonia, pneumothorax, ECMO, renal replacement therapy, inhaled vasodilators, airway pressure release ventilation and tracheostomy.

How is study monitoring arranged?

Study monitoring will be arranged by the participating site according to the local regulations.

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