Case study: Seeking effective alternatives to mechanical ventilation for COVID-19 patients - the RECOVERY-Respiratory Support Trial
Patients with severe symptoms of COVID-19 who may be struggling to breathe may require help to get more oxygen into their lungs. At the start of the pandemic, patients may have been treated with a ventilator in intensive care units or with a less invasive method of respiratory support.
By identifying which non-invasive treatments are most effective, and using these at an earlier stage, it was believed it may be possible to reduce the need for invasive mechanical ventilation, and therefore keep more patients out of critical care wards.
In spring 2020, three methods of non-invasive treatment are already being used in the NHS to treat patients with COVID-19. However, as this YouTube video about the Recovery RS trial explains, at the time it was not known which would be the most effective in the long term. In fact, recommendations for non-invasive treatments for COVID-19 patients across the globe were inconsistent.
As more patients were treated during the pandemic, some clinicians found non-invasive treatments helpful whilst others were concerned it delayed intubation, potentially causing harm. The existing evidence was not robust enough to reliably confirm which treatment had the greatest benefit and least risk to patients. Only with high-quality data from a randomised control trial would researchers be able to demonstrate which treatment truly has the best outcomes for patients and inform clinical practice going forward.
It is for this reason that the RECOVERY-RS trial (Randomised Evaluation of COVID-19 Therapy - Respiratory Support) was set up.
The trial was funded and supported by the NIHR, and was one of a number of COVID-19 studies that are considered to be urgent public health research by the UK’s Chief Medical Officers. It was given priority status by the Department of Health and Social Care through the NIHR’s national prioritisation process. It was strongly supported by the NIHR’s Clinical Research Network (CRN) including the West Midlands CRN Study Support Service, and national speciality groups for respiratory disorders and critical care.
RECOVERY-RS is the world’s largest non-invasive respiratory support trial for COVID-19 - with over 1,200 patients with acute respiratory failure taking part across 48 UK hospitals, between April 2020 and May 2021.
The research compared three existing non-invasive treatments to determine which provides the best long-term outcome for patients. These treatments are:
- Continuous Positive Airway Pressure (CPAP) - where a patient wears a tightly fitted face mask through which a mild to high air pressure is applied on a continuous basis to keeps the airways open;
- High Nasal Flow Oxygen (HFNO) - where a patient receives humidified (moistened) and warmed oxygen through tubes into the nose;
- oxygen therapy - where a patient wears a normal face mask or tubes in the nose to receive oxygen.
Trial participants were randomly allocated to one of these three treatments.
The primary outcomes assessed through the trial were whether the patient went on to require tracheal intubation (invasive mechanical ventilation, where a tube is inserted into a patient's throat to help them breathe) or died within 30-days of beginning treatment through the trial.
Aware of the pressures on hospitals and NHS teams, the research was designed to create minimal burden on sites that take part. The trial was flexible as not all the treatments had to be delivered at every site, patients could be recruited from any part of the hospital, data collection was minimised, and it was also possible to co-enrol with other COVID-19 studies.
Of the 1,272 participants, 29.9% received CPAP, 32.8% received HFNO and 37.3% received conventional oxygen therapy.
Data from RECOVERY-RS shows that patients treated with CPAP were less likely to need mechanical ventilation or die within 30 days of beginning treatment, compared with participants 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.
Not only is this beneficial for patients but also reduces the burden on NHS resources for mechanical ventilators and critical care beds.
Preliminary data from the trial also suggested that there was no difference in primary outcomes between patients in the HFNO and conventional oxygen therapy groups.
Delivering the RECOVERY-RS trial: the research teams' perspectives
The study has been led by passionate researchers, urgently seeking answers for patients.
Reflecting on the results, Professor Danny McAuley, Co-Chief Investigator, based at Queen’s University Belfast said:
"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 Gavin Perkins, Co-Chief Investigator, based at the University of Warwick Clinical Trials Unit added:
“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.”
Teams across the country were involved in delivering the study and many found taking part a valuable experience.
Dr Jay Naisbitt, a Consultant in Intensive Care medicine, was a Principal Investigator on RECOVERY-RS. He found that integrating research into routine practice has facilitated patient recruitment into urgent public health studies and has boosted morale across his team. Read Jay's blog on the multi-fold benefits of integrating research in standard care.
Heather Willis, a Research Nurse at Good Hope Hospital, has been working on the frontline, delivering urgent public health research, during the pandemic. Her experience working on the RECOVERY-RS trial has reinforced her views that research makes a real difference to patient lives and is best delivered as part of a team. Read Heather's blog, "Removing the cloak of invisibility".
Taking part in the trial: a patient's perspective
Phil Cawkwell, now 39, was hospitalised with COVID-19 in early April 2020. Struggling to breathe, he was grateful to have the chance to take part in the RECOVERY-RS trial and hoped he’d be able to help other people as a result. While recovering at home but still feeling the effects of the virus, he told us his story. Read Phil's COVID-19 research story.
“I am incredibly grateful I was offered the chance to take part in the trial. It’s a fantastic opportunity and gives you hope at a dark time to think you might be helping other people. I have always been interested in research and I would say to anyone who gets the chance - just do it.”
Read more about our response to the COVID-19 pandemic.