Dr Ben Prudon, respiratory consultant at University Hospital of North Tees, reflects on the experience and impact of early involvement in the RECOVERY trial for patients with COVID-19.
The COVID-19 pandemic has had a profound effect on every nation, with individual freedoms previously taken for granted having to be curtailed as governments and public health teams grapple with limiting the rate of spread. Clinical teams, used to working in pressurised and under-resourced settings, have stepped up again, this time to the challenge of providing the healthcare needs of patients and colleagues who have caught COVID-19. Sadly, far too often the final resort has been to do our best to ensure a comfortable death for patients whose lungs have been damaged by the virus. I, like many others, will continue to remember certain faces for many years to come.
However, the pandemic has been the catalyst for an evolution of several aspects in healthcare: interdepartmental and organisational partnership, telemedicine, use of Microsoft Teams, and research. Evidence-based medicine has always been at the forefront of modern NHS practice, but research participation within the ‘shop floor’ has often remained in the corner, with the majority of clinicians seeing this as something actually performed by those with a special interest, dedicated time, and sitting in a tertiary unit. COVID-19 has changed this.
In early 2020, no specific COVID-19 treatment existed. That was difficult and uncomfortable for us as clinicians used to ensuring patients get access to the best quality proven treatments. Reports emerging from China, Italy and the White House suggested several existing medications could be useful – but what do you do for your individual patient – pick one at random, use them all, or ignore them all and concentrate on supportive care?
As the NHS began to realise the challenges that were coming, our world-class national research infrastructure started to act. In February, the National Institute for Health Research (NIHR) launched a £20 million rapid response fund, in addition to funding set-aside for vaccine development. The RECOVERY trial (Randomised Evaluation of Covid-19 Therapy) run by Oxford University was one of the projects to receive funding and has been the most influential trial to date.
The RECOVERY trial was designed to be a pragmatic and adaptive trial assessing the impact of treatments for patients requiring hospital treatment for COVID-19. It was designed to be rolled out rapidly across hospitals with minimal barriers for patient and clinician participation. The central team developed an uncomplicated web-based educational and randomisation platform, with supportive video meetings for collaborators. Starting with exploring the use of hydroxychloroquine, lopinavir-ritonavir, and dexamethasone, Oxford recruited their first patient on 19 March, and at the University Hospital of North Tees we began recruiting from 30 March.
Everyone understood that to move forward with COVID-19 management, we needed as many patients involved as quickly as possible. There was no point in a trial that produced results after the pandemic had ended! At North Tees and throughout the UK all grades of doctors leapt at the chance to become involved in RECOVERY. Research had moved out of the periphery. All grades of doctors became directly involved in patient discussion and consent. There was a complete acceptance that for an individual patient, and the population as a whole, taking part in research was the right thing.
Within our hospital we achieved significant success at maintaining high patient recruitment into RECOVERY, peaking at almost 65% of patients admitted. This was achieved through a fantastic clinical team effort supported by our research nurses. The nurses have supported clinical teams in all aspects of the trial, and have maintained a 7-day service since our first patient. We have also been fortunate to have been supported by a highly energised R&D administrative team and dynamic pharmacy.
By summer 2020, RECOVERY had established that lopinovir-ritonavir and hydroxychloroquine had no impact on hospital outcomes. But the cheap and cheerful corticosteroid dexamethasone was a life saver – the sicker the patient, the more impact it had. This is now a standard aspect of care throughout the world. The mortality rates already appear lower and RECOVERY may be directly responsible for this. Clearly further advances are still needed. RECOVERY is now into version 12, and is exploring the use of colchicine, aspirin, tocilizumab, convalescent plasma, and the monoclonal antibody treatment REGN-COV2.
REGN-COV2 is an exciting addition to RECOVERY as the first manufactured COVID-19 specific treatment. Safety and laboratory data looks promising – but does it actually help hospitalised patients? At North Tees, due to our successful recruitment we were one of the first sites to receive the drug, and after a fantastic team effort we were first in the country to start administering it to patients.
Until the vaccines start having a meaningful effect on hospital admission numbers, clinical teams will continue to focus on improving care for patients admitted with COVID-19. Research is now centre stage.