NIHR Respiratory Translational Research Collaboration develops new trial to find the first medication for long-COVID

In 2020, the COVID-19 pandemic caused worldwide disruption, panic and uncertainty. For some, COVID-19 was life-threatening and, in some cases, fatal. It also soon became apparent that some people with COVID-19 experienced long-lasting effects. This is now known as “long-COVID”. Common symptoms of long-COVID include fatigue, breathlessness, brain fog, palpitations and headaches. For many, daily lives, work lives and social lives are disrupted. Generally, patients with long-COVID no longer feel like themselves. The causes of long-COVID are being investigated, but some people appear to have ongoing inflammation in the body. This is where normal bodily processes become disrupted. 

To better understand long-COVID, the NIHR Respiratory Translational Research Collaboration (R-TRC), along with 5 other NIHR TRCs, joined forces to establish a national consortium. A research study was designed aiming to integrate research and clinical service. Its purpose was to understand and improve long-term outcomes for survivors of hospitalisation with COVID-19. This study is known as the PHOSP-COVID (Post-Hospitalisation COVID) study. 

Widely used medicine is tested to help reduce symptoms of long-COVID

Findings from PHOSP-COVID have shown there to be a link between the severity of ongoing health impairments and inflammation. It was proposed that reducing levels of inflammation may improve long-COVID symptoms and therefore quality of life. One well-known anti-inflammatory medication identified was Tocilizumab. This is currently used to treat rheumatological conditions. 

The PHOSP-Inflammation (PHOSP-I) study was established to test whether Tocilizumab will improve symptoms and health-related quality of life in people living with ‘inflammatory’ long-COVID. It was designed in partnership with patients and the public. This was to ensure the patient perspective was at the heart of the aims, design and conduct of the study. Tocilizumab will be administered via an injection at regular intervals over 12 weeks. Participants will then be followed for 3 months after their last injection. Various outcomes will be measured at the start of the study, at the end of treatment and at the end of their follow-up period. The main outcome is whether people feel better after the intervention. This will be assessed by a questionnaire which assesses health-related quality of life.

Professor Rachael Evans, consultant respiratory physician at Glenfield Hospital, Leicester, Professor at the University of Leicester and member of the NIHR R-TRC explained the potential benefits of the PHOSP-I trial. She said:

“We're looking for a medicine that can be used in a clinic to help patients with long-Covid within five years, that’s the number 1 goal. We are also taking samples from the trial to create a bioresource. This will enable us to learn more about the underlying mechanistic pathways that are driving inflammation and, if the trial is successful, leading to improvements in symptoms. This is the second goal.” – Professor Evans

The NIHR Respiratory TRC supports the development of PHOSP-I

Professor Evans praises the NIHR R-TRC for the support provided to her in developing the PHOSP-I trial protocol. The R-TRC enabled Dr Evans to gain advice and support from various academics and clinicians in the field. She said:

“Via the R-TRC, I was able to get advice and learn from others. Having that wealth of experience of people that have designed, run and delivered experimental medicine trials all in one room was invaluable.” - Professor Evans

Additionally, the R-TRC enabled Professor Evans to expand the number of sites that PHOSP-I is open at. The R-TRC is made up of clinical academics from across 10 NIHR Biomedical Research Centres. This meant Professor Evans could promote the trial to centres across the UK via R-TRC membership meetings. She emphasised how valuable the R-TRC was in enabling such a large number of sites to be involved in such a complex trial:

“It would take years to try and pull together 15 sites with people that you've never worked with to run the PHOSP-I trial. Instead, I was able to present it at Respiratory TRC meetings where each TRC member could express willingness and their ability to participate.” - Professor Evans

Additional sites were identified via the NIHR Clinical Research Facilities (CRFs). Professor Evans notes how the R-TRC badge enabled her to contact and discuss PHOSP-I with senior directors within the NIHR CRFs. Professor Evans believes that the R-TRC badge and knowledge that the proposal had been approved by a team of people led her to successfully recruit more sites to PHOSP-I. PHOSP-I is funded by Genentech Roche. Dr Evans highlights that having 15 sites to deliver the trial made it much more attractive to get Genentech Roche on board.

Next steps

A total of 152 participants are planned to be recruited to the trial across 15 sites. They will be randomly assigned to receive either Tocilizumab or a placebo. If the PHOSP-I trial is successful and long-COVID patients are responding positively to Tocilizumab, the next stage will be to carry out a Phase 3 trial. This will involve testing Tocilizumab in a much larger group of people. 

Find out more information on the study, and discover the previous findings of PHOSP-COVID.