A new national trial is aiming to use pandemic lessons to help quickly find effective treatments for people hospitalised with severe flu.
There may be record numbers of flu cases this winter, and there is no clear evidence about which treatments are best for severe cases. Although many people with flu get better on their own without needing hospital treatment, it can make some people seriously ill and even be life-threatening.
The £2.9 million REMAP-CAP trial will work with the National Institute for Health and Care Research (NIHR) to recruit children and adults hospitalised with severe flu from 150 hospitals across the UK over the next two years. It will be run by researchers and clinicians from Imperial College London and Imperial College Healthcare NHS Trust in collaboration with other national experts. It is funded by the NIHR and delivered by the NIHR's Clinical Research Network.
This is the first time a trial of this kind will be used for flu. The REMAP-CAP trial was originally set up to tackle pandemics. It is exactly two years since REMAP-CAP showed in COVID-19 how reducing inflammation with the drug tocilizumab can save lives in severely ill patients.
The trial is designed to provide answers quickly by using a robust yet rapid approach to test multiple treatments at the same time in thousands of people. The trial will be highly adaptive, allowing the team to learn quickly from early results and ensure people are given treatments that show encouraging results as soon as possible.
Professor Anthony Gordon, Chief Investigator of the new trial, from Imperial College London’s Department of Surgery and Cancer and Consultant in Intensive Care Medicine at Imperial College Healthcare NHS Trust, said: “During the pandemic, our trial was able to rapidly respond to a new virus and our approach helped save lives. We’re now redeploying it against a known threat. Flu is very infectious and can make children, the elderly and vulnerable people seriously unwell in some cases.
“This winter, we might see more flu cases than usual as the virus potentially resurges after pandemic measures have kept levels low. We hope that our trial will help to find urgently needed flu treatments rapidly. Our COVID-19 trial changed clinical practice globally, and we hope we can impact flu treatment and reduce winter pressures on the NHS in the same way.”
Running for two years (in the first instance), the trial aims to recruit several thousand people, and will test multiple treatments. These include the anti-viral treatments oseltamivir (also known as Tamiflu) and baloxavir, as well as steroids and anti-inflammatory drugs that were found to be effective against COVID-19 in the original REMAP-CAP trial. More treatments may be added in the future.
The trial will be open to adults, children, and babies over the age of one month who are hospitalised with severe flu. Children and babies will receive lower treatment doses than adults.
Dr Elizabeth Whittaker, a Consultant in Paediatric Infectious Diseases at Imperial College Healthcare NHS Trust and a Senior Clinical Lecturer in the Department of Infectious Diseases at Imperial College London, is leading the children’s part of the trial. She said: “Flu can be a very serious illness for some children, in some cases leading to hospitalisation and problems like bronchitis and pneumonia.
“Getting the free spray flu vaccine is our first line of defence and drastically reduces the risks for children. But we also need more treatments to help those children who do become very ill, which is why this trial is so important.
“Working with a range of experts across the country, we hope to determine the best treatments for flu and ultimately save lives.”
Minister for Health and Secondary Care Will Quince, said: “Clinical research was vital in our fight against Covid and helped to save thousands of lives across the country.
“This innovative trial will use the lessons we learned from Covid and deliver treatments to reduce serious illness in patients with flu, ease pressure on the NHS and ultimately save lives.
“While this trial aims to prevent illnesses for future flu seasons, we are now seeing increased levels of flu this year, and it is vital that all those eligible for a free vaccine come forward as soon as possible.”
The researchers will study how effective the treatments are at reducing deaths from flu and stopping patients needing intensive care.
To help them to determine which treatments provide the best use of NHS resources, the researchers will also monitor whether the treatments reduce severe symptoms, stop people needing breathing support, and shorten the amount of time people stay in hospital or intensive care. The researchers will also measure quality of life and disability after recovery.
The trial brings together leading UK experts including specialists in intensive care, respiratory medicine, and children’s medicine. It will also involve experts in infectious diseases and virology who will carefully monitor to see if the flu virus becomes resistant to any of the anti-viral drugs tested in the trial.
Unlike other trials, which usually test individual treatments for a set amount of time, the new trial – known as an adaptive platform trial – continues as new treatments are added. Any treatments which are found not to work will be removed. It will also involve trialling the treatments alone, in combination, and for different durations to find the best way to treat flu.
“Using this approach, we can bring in new treatments and test them thoroughly against one another without having to stop and start trials. Typically, you’d need a new trial for every treatment, which takes time. Instead, this type of trial keeps research rolling,” explained Professor Gordon. Patient groups have helped design this trial platform through workshops and interviews.
Professor Paul Dark, Deputy Medical Director, NIHR Clinical Research Network said: "The scale of this study, requiring us to co-ordinate patient involvement across at least 150 NHS acute hospitals, is a huge undertaking that draws on the UK's world-leading research infrastructure.
"Taking part in research saves lives and benefits us all, both now and in the future. We really encourage everyone to be part of research."