A new study is testing a potential treatment for some of the most seriously ill Covid-19 patients.
Experts from Salford Royal NHS Foundation Trust (part of the Northern Care Alliance NHS Group), Manchester University NHS Foundation Trust (MFT) and The University of Manchester have joined together for the research which aims to help critically ill patients on ventilators. The first patient in the UK started the study at Salford Royal in June and the team aim to involved 40 patients overall.
Data suggests that some patients have a hyperinflammatory response in response to the infection and these have a higher risk of becoming critically ill and dying.
The new study will test two ways of giving an existing approved anti-inflammatory drug, Anakinra, to these patients.
Anakinra is a cytokine blocker (antagonist). It works by blocking the actions of an inflammatory molecule (a cytokine) called Interleukin-1 (IL-1) which is part of the body’s defences and naturally produced to combat a range of illnesses. In Covid-19 the body’s defences overreact producing a cytokine storm. It is this cytokine storm that causes the severe respiratory disease and other organ failure that puts people in ICU and causes death. The team believe using a cytokine antagonist such as Anakinra could prevent the cytokine storm and thereby potentially reduce or even prevent severe Covid- 19.
The treatment has previously been used safely in critically ill patients and has reduced mortality in patients with severe infections and high levels of inflammation.
The Greater Manchester study will take place at Salford Royal, part of the Northern Care Alliance and Manchester University NHS Foundation Trust ‘s Manchester Royal Infirmary and Wythenshawe Hospital. It is funded by a combination of research funds from the Northern Care Alliance and the National Institute for Health Research Manchester Biomedical Research Centre and sponsored by The University of Manchester.
It will compare giving Anakinra four times daily via an intravenous infusion with giving a twice-daily injection under the skin. In both arms of the study, patients will continue on the treatment for 14 days or until they no longer need to stay in critical care. Up to 40 patients will take part.
The Chief Investigator for the study is Dr Tim Felton, Consultant in Intensive Care and Respiratory Medicine at MFT and Senior Lecturer in the Division of Infection, Immunity and Respiratory Medicine at The University of Manchester (pictured above right).
He said: “Anakinra is highly effective in treating overreactive immune response and severe infections. Because of this it could prove effective in treating Covid-19 patients, and several global trials are now underway to investigate this. The drug is typically administered as an injection either into the vein or under the skin. We think injection under the skin is a more efficient way of delivering the drug and that’s why with SCIL-1Ra we want to compare the two methods. We hope to show one method is more effective than the other and deliver better outcomes for patients. ”
The study is based on long standing research in the role of cytokines in all forms of stroke and the role of Anakinra in reducing the severity of the stroke and improving outcome.
This research has involved successful collaboration between neurosurgeons and stroke physicians in the Manchester Centre for Clinical Neurosciences at Salford Royal and neuroscientists at The University of Manchester into inflammation in stroke.
Professor of Neurosurgery at the University and Consultant Neurosurgeon at Salford Royal Professor Andrew King added: “While it might seem unusual that a group of neurosurgeons and neuroscientists are involved in Covid research, our expertise in Anakinra, including clinical trials of it in various forms of stroke, puts us in an ideal position to propose repurposing the drug to reduce the cytokine storm that causes so much harm in Covid-19. If we can block this cytokine storm we can potentially reduce and even stop the lung inflammation that puts people in ICU and causes so many deaths. Our experience in stroke is that the drug works effectively given twice a day and subcutaneously (under the skin). The national trial of Anakinra, REMAP-CAP, is four times a day and intravenously (into a vein). If it were true that the twice daily subcutaneous regime was effective in Covid-19, and there is good reason to think it is, then Anakinra could potentially be given to twice as many people and by a simpler and less resource demanding method.”
Professor King (pictured above left) is one of a team of researchers – including neurosurgical colleagues at Salford Royal Mr Hiren Patel and Mr Omar Pathmanaban and colleagues at The University of Manchester Prof Stuart Allan, Prof Dave Brough and Prof Andy Vail.
They have contributed to the global conversation about this potential treatment and their analysis of the best way forward for Anakinra in Covid-19 was published in the leading medical journal Lancet Rheumatology as part of The Lancet Covid-19 resource centre.