Published: 05 August 2021
- Landmark UK trial compared three commonly used respiratory interventions to establish which works best for COVID-19 patients with acute respiratory failure.
- Participants who received continuous positive airway pressure (CPAP) were less likely to require invasive mechanical ventilation from COVID-19.
- Researchers found no benefit from high flow nasal oxygenation (HFNO) over standard oxygen therapy.
- Based on this evidence, the authors say CPAP should be considered for hospitalised patients with COVID-19 needing increasing oxygen - reducing the need for invasive ventilation and relieving pressure on intensive care services.
The NIHR-supported Respiratory Strategies in COVID-19; CPAP, High-flow, and Standard Care (RECOVERY-RS) trial has demonstrated that treating hospitalised COVID-19 patients who have acute respiratory failure with continuous positive airway pressure (CPAP) reduces the need for invasive mechanical ventilation.
Preliminary data from the trial also suggests that the routine use of high flow nasal oxygenation (HFNO), which can consume large amounts of oxygen, should be reconsidered as it did not improve outcomes for COVID-19 patients compared with conventional oxygen therapy.
RECOVERY-RS, led by the University of Warwick and Queen’s University Belfast, is the world’s largest non-invasive respiratory support trial for COVID-19 - with over 1200 participants taking part across 48 UK hospitals. The multi-centre, adaptive, randomised controlled trial compared the use of CPAP (oxygen and positive pressure delivered via a tightly fitting mask), with HFNO (high pressure oxygen delivered up the nose), against standard care (standard oxygen therapy).
All three interventions are commonly used to treat COVID-19 patients before they are moved onto invasive ventilation in a critical care bed, but it was not known which, if any, resulted in better outcomes.
Over 13 months, between April 2020 and May 2021, a total of 1,272 hospitalised COVID-19 patients with acute respiratory failure, aged over the age of 18, were recruited to the study and randomly allocated to receive one of three respiratory support interventions as part of their hospital care.
380 (29.9%) participants received CPAP; 417 (32.8%) participants received HFNO; and 475 (37.3%) received conventional oxygen therapy.
The primary outcomes assessed through the trial were whether the patient went on to require tracheal intubation (invasive mechanical ventilation) or died within 30-days of beginning treatment through the trial.
In the comparison of CPAP and conventional oxygen therapy, the likelihood of patients going on to require invasive mechanical ventilation or die within 30-days of treatment was significantly lower in those who were treated with CPAP, than those who received standard care. In the CPAP group, 137 of 377 participants (36.3%) either needed mechanical ventilation or died within 30 days, compared with 158 of 356 participants (44.4%) in the conventional oxygen therapy group.
There was no difference in primary outcomes between patients in the HFNO and conventional oxygen therapy groups. In the HFNO group, 184 of 414 participants (44.4%) went on to require mechanical ventilation or die, compared with 166 of 368 participants (45.1%) in the conventional oxygen therapy group.
Based on these results, 1 person would avoid needing invasive ventilation within intensive care units (ICU) for every 12 people treated with CPAP instead of standard oxygen therapy.
Professor Gavin Perkins, Chief Investigator and Professor in Critical Care Medicine at Warwick Medical School at the University of Warwick said: “The RECOVERY-RS trial showed that CPAP was effective at reducing the need for invasive ventilation, thus reducing pressures on critical care beds. The routine use of high flow nasal oxygenation, which can consume large amounts of oxygen, should be reconsidered as it did not improve outcomes. By giving patients the most effective treatment to begin with, we can help prevent resource shortages in our NHS and make sure the right type of ventilation is available to patients when it is required.
“This is the first large trial of different types of ventilation in COVID-19. While it is encouraging that these results can help reduce the number of people who require invasive ventilation, it is important to stress that, where it is needed, invasive ventilation can be lifesaving.”
Professor Danny McAuley, Chief Investigator and Professor and Consultant in Intensive Care Medicine at the Royal Victoria Hospital and Queen's University Belfast said: "Over the COVID pandemic, we've seen a large number of patients requiring high levels of oxygen and admission to ICU for invasive ventilation, causing a huge strain on staff and beds.
"The results of this trial are really encouraging as they have shown that by using CPAP, invasive ventilation may not be needed for many patients with COVID-19 requiring high oxygen levels. Avoiding invasive ventilation is not only better for the patients, but it also has important resource implications as it frees up ICU capacity. This research should help healthcare professionals in the UK and beyond manage patients with COVID-19, to improve patient outcomes while helping to lessen the burden on resources."
Professor Jonathan Van-Tam, Deputy Chief Medical Officer said: “COVID-19 has placed huge pressure on our hospitals and intensive care units, and our doctors, nurses and all NHS staff have stepped up to meet that challenge. A key part of tackling COVID has been the improvements that staff have identified and then implemented in terms of how to best care for COVID patients.
“This study, funded by the NIHR, provides valuable evidence around how non-invasive respiratory support can be used to improve patient outcomes. Reducing invasive mechanical ventilation is better for patients and reduces pressures on mechanical ventilator capacity across the NHS.
“I want to thank the team of doctors, researchers and patient volunteers involved in today’s excellent results – hospitals across the country can now use these data to further improve care for patients and reduce the demand for mechanical ventilation as we get closer to what might still be a challenging winter period.”
Professor Lucy Chappell, Chief Scientific Adviser (CSA) for the DHSC and the NIHR Chief Executive Officer, said: “Research such as this has been a huge asset to the COVID-19 response, allowing us to fine-tune our approach and improve care for patients in hospital.
“I am hugely grateful to the teams at the University of Warwick and Queen’s University Belfast for their contribution to our understanding of the virus through this NIHR-funded study, and particularly how to treat it.
“This data will help ensure hospitalised patients with COVID-19 get the best possible care, making a difference to patients and intensive care units across the country.”
Professor Nick Lemoine, Medical Director at the NIHR Clinical Research Network said: “Preliminary results from this NIHR-supported trial provide important evidence which will help shape clinical practice worldwide around respiratory support interventions for hospitalised COVID-19 patients. The study will undoubtedly help improve outcomes for patients - while potentially alleviating pressure on hospital beds and critical care services.
“We sincerely want to thank everybody involved - the patients who took part in their darkest hour, and the NHS doctors and nurses who helped deliver the study right across the UK.”
Professor Simon Ball, Executive Medical Officer at University Hospitals Birmingham said: "This is an important study that will significantly influence treatment decisions. It is an example of how well NHS hospitals can deliver studies to improve clinical practice. This includes the definition of treatments that are beneficial, in this case CPAP, but just as importantly those with no apparent benefit, in this case high flow nasal oxygen. The best possible care we deliver is that focused by evidence.”
Both CPAP and HFNO have been widely used worldwide in the management of COVID-19 throughout the pandemic for patients who need high levels of additional oxygen. If these treatments are not successful, patients need to be sedated and treated with a ventilator in intensive care. Although both CPAP and HFNO are commonly used in other lung conditions, prior to the RECOVERY-RS study, it was unknown how safe and effective they were for people with breathing difficulties arising from COVID-19.
The trial is led by Joint Chief Investigators Professor Gavin Perkins at the University of Warwick, and Professor Danny McAuley at Queen's University Belfast. It was funded and supported by the NIHR as a prioritised urgent public health COVID-19 study.
RECOVERY-RS was one of the first COVID-19 studies to be classed as urgent public health research by the UK’s Chief Medical Officers in order to urgently identify strategies to reduce the need for invasive mechanical ventilation. Launched in April 2020 as COVID-19 hospitalisation began to soar, the NIHR Clinical Research Network provided prioritised research delivery support to rapidly set the study up at hospital sites across the UK and enroll participants. The NIHR’s research infrastructure, expertise and delivery support has been critical to the trial’s success.
The preliminary results of this evaluation of the data will be available as a pre-print on medRxiv on 5 August 2021 and will be submitted to a leading peer-reviewed medical journal. The results will be presented in detail at a free virtual Critical Care Reviews conference session on Thursday 5 August at 7.30pm.
Taking part in RECOVERY-RS: Lisa's story
Lisa Broadhurst, 42, from Birmingham, took part in the RECOVERY-RS trial in January after contracting COVID-19.
She was rushed to hospital by ambulance on 13 January with breathing problems and dropping oxygen levels, 11 days after first experiencing symptoms of aches and pains, loss of taste and smell and a severe headache.
Diagnosed with severe COVID-19 and pneumonitis, Lisa, who is also asthmatic, said: “I’ve never been so scared in my life. I had no control of my deteriorating health. I remember Face Timing my family and letting them know how poorly I was. All I could think about was whether I’d go home or whether covid would kill me like so many other patients. The nurses would squeeze my hand and reassure me to stay strong. It was a heartbreaking time and I wouldn't wish that feeling on anyone.”
Lisa, who received CPAP as part of the trial, remembers being connected to the machine: “The pressure of the oxygen took a little while to get used to. It was a scary experience and took my breath away at first. All I could think about was making it home to my family. I fought as hard as I could to stay alive, I cried a lot and I was scared and overwhelmed.
“But throughout the time on the machine I could see I was getting better. It was the best feeling ever leaving the hospital and walking outside into the fresh air knowing I was going home to my loved ones.”
COVID-19 still has a lasting impact on her health and her lungs are much more sensitive.
But she added: “I’m extremely grateful I took part in the trial - the level of care I received from everyone was amazing. The nurses and doctors showed so much support. I couldn’t have asked for better and taking part in the trial saved my life. I will always forever be in debt to the NHS - they helped me to go back home to my family. Research really does help benefit others and it’s the reason I’m alive today.”
Find out more
- Participant case study: "Just Do It" - Phil’s COVID-19 Research Story
- Case study: Seeking effective alternatives to mechanical ventilation for COVID-19 patients - the RECOVERY-Respiratory Support Trial
- Full details of the study protocol and related materials are available on the University of Warwick website