A study to see whether the lungs of very sick patients on an artificial lung machine heal more quickly with slower, deeper breathing

Plain English summary of protocol

Background and study aims
Acute Respiratory Distress Syndrome (ARDS) is a serious condition where the lungs become inflamed and injured, making it difficult for the body to get enough oxygen. This happens for many reasons, like infections (such as pneumonia), trauma, sepsis, or pancreatitis. ARDS can happen to anyone, no matter their age, and it’s a major cause of death, with survival rates lower than 60%. For those who survive, the recovery can be long and tough, with lasting effects like difficulty exercising, mental health struggles, and a lower quality of life that can last for years. A study of intensive care units (ICUs) across 50 countries found that about 10% of ICU patients develop ARDS, and 23% of those who need a ventilator end up with the condition.
Ventilators can help save lives, but they can also cause more damage to the lungs (called ventilator-induced lung injury or VILI). To reduce this damage, doctors use techniques like lower air pressure or placing patients on their stomachs. Still, some ARDS patients continue to worsen despite these efforts and need extra support through a treatment called veno-venous extracorporeal membrane oxygenation (VV-ECMO). This involves a machine that takes over the oxygen exchange in the body, allowing doctors to reduce the need for the ventilator and further lung damage. Unfortunately, there are no specific drugs to treat ARDS yet, and the focus remains on supporting the patient and treating the cause of the condition.
The positive effects of using a lung protection strategy during ventilation and supporting patients with VV-ECMO (a machine that helps with oxygen exchange) in ARDS have been clearly shown to improve survival. Patients who need ECMO typically have the most severe form of ARDS and are still at risk for further lung damage, even when doctors try to reduce the intensity of the breaths they receive. Right now, doctors use a lung protection strategy that reduces the amount of air pushed into the lungs, keep the pressure low and try to keep the lungs open. This is considered the standard of care. But there’s still a lot of uncertainty around the best way to ventilate ARDS patients who are also on ECMO, because no large, well-designed clinical trial has yet determined whether current strategies are fully protecting the lungs from damage. As the use of ECMO is growing worldwide, more research is urgently needed to figure out the best ventilation practices for these patients, with the goal of reducing the time they need ECMO, lowering the risks of complications, and improving survival rates.
For the most severely affected ARDS patients who require ECMO, the best way to minimize ventilator-induced lung injury (VILI) is by reducing the frequency of breaths, as this is the main factor contributing to lung damage. This would allow the ECMO machine to handle the majority of the gas exchange. Some studies have looked into using complete apnoeic ventilation (where the ventilator doesn’t breathe for the patient at all) to achieve this. However, the key issue is that the use of complete apnoea, means the lungs aren’t being ventilated, and they can collapse, leading to atelectasis (lung tissue collapse). When ventilation is resumed, this can make it harder to re-expand the lungs and can even increase the risk of further injury due to high pressure or stress on the lung tissue. Additionally, when the lungs are inactive for too long, this can lead to poor lung compliance, meaning the lungs don't expand and contract as easily, which makes mechanical ventilation harder to manage.
Near apnoeic ventilation (NAV), offers a balanced approach: it keeps lungs almost at complete rest (minimizing ventilator-induced injury), but uses a few deeper breaths each minute (called sigh breaths) to maintain lung openness and reduce uneven stress across the lung and avoids lung collapse. This approach could help ARDS patients on ECMO recover faster, potentially reducing ECMO time, ventilator duration, and ICU stays—though more research is needed to confirm these real-world outcomes.
The aim of our study is to test if near apnoeic ventilation in ARDS patients on ECMO with just two sigh breaths per minute is better than what doctors use at the moment, which is varied between 10 and 30 breaths per minute. We hope that using only two deep sigh breaths will allow the lungs to recover quicker and patients will need less time receiving ECMO and mechanical ventilation reducing the risks of VILI.

Who can participate?
Patients aged 18 years and over in the ICU receiving invasive mechanical ventilation for severe ARDS being considered for ECMO

What does the study involve?
A participant in the study, will be randomly assigned to one of two groups by chance (like flipping a coin). They may not know which group they were allocated, but the study doctor and team will know. One group will receive two sigh breaths and the other normal standard ventilation while on ECMO. They will receive this ventilation method for the first three days on ECMO and then it will be up to the clinical team to decide on continuing with the two breaths or, if the lungs are recovering, to return to usual settings on the ventilator.
A participant will also be asked if they agree to blood and lung fluid samples being collected. These samples will allow us to investigate how the different types of ventilation affect the patient and better understand ARDS and how the ventilator damages the lungs more fully.
The doctors and nurses will also record ventilator and ECMO settings and patient observations, for example blood pressure, and document the medications and treatments they give the participant as part of their routine care. The research team will collect some of this data where relevant to this study.
Participants will be followed up by the clinical research team daily whilst in ICU. Once the participants have left the ECMO ICU and been discharged to the referring hospital, they will be followed up prior to hospital discharge from the referring hospital. Follow-up at 6 and 12 months will be via either electronic/postal/telephone questionnaires, medical records and data linkage with NHS Digital (eDRIS in Scotland) records wherever possible.

What are the possible benefits and risks of participating?
We cannot promise that the study will benefit the person participating in the study but the information we get from this study may help patients in the future. Their involvement in the study may help us understand and reduce the possible complications associated with mechanical ventilation whilst on ECMO support. Their biological samples and data could improve our understanding of ‘restful’ and ‘moderate’ support to a patient’s breathing.
The risks of being on two breaths per minute from the ventilator is low as the function of the lungs is completely taken over by the ECMO machine. Risk is low from biological sampling – samples are taken alongside routine clinical blood samples using the same blood lines that have already been connected to the participant's body. Bronchoscopy is a standard procedure performed on ICU to obtain lung fluid samples

Where is the study run from?
Imperial College London (UK)

When is the study starting and how long is it expected to run for?
June 2024 to October 2029

Who is funding the study?
National Institute of Health Research Efficacy and Mechanism Evaluation (EME) Project: NIHR158537 (UK)

Who is the main contact?
1. Dr Sharon Mumby, romeo@imperial.ac.uk
2. Dr Brijesh Patel, romeo@imperial.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• Scotland
• United Kingdom

Study participating centres

Sponsor information

Imperial College London
University/education

Research Governance and Integrity
Level 5
Sherfield Building
London
SW7 2BB
England
United Kingdom

Email	a.ndoutoumou@imperial.ac.uk
Website	https://www.imperial.ac.uk
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

Government

Results and Publications

Editorial Notes

08/09/2025: Study's existence confirmed by the NIHR.