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New studies reinforce evidence that corticosteroids improve survival rates among critically ill COVID-19 patients

 

Four papers published today on the use of corticosteroids to treat COVID-19 have reinforced evidence that outcomes for severely affected patients can be significantly improved by using these inexpensive and widely available drugs, with one paper suggesting the risk of death can be reduced by up to 20%.

The papers - simultaneously published in the Journal of the American Medical Association (JAMA) - include findings from the REMAP-CAP study being conducted across 15 countries, around the world and for which the NIHR’s Clinical Research Network and partner research institutes from devolved nations recruited close to 71% of all study participants. 

The REMAP-CAP findings shows a high probability that, among critically ill patients with COVID-19, treatment with a seven-day course of hydrocortisone improved outcomes such as survival and more rapid recovery compared with no hydrocortisone treatment.

Another paper, co-ordinated by the World Health Organisation (WHO) and led by researchers at the University of Bristol and the NIHR’s Bristol Biomedical Research Centre, provides a meta-analysis (evidence summary) of global steroid use across seven randomised controlled trials (RCTs) in 12 countries spanning five continents. It also included data drawn from REMAP-CAP and the NIHR-funded RECOVERY trial, which has already shown that the steroid dexamethasone can be successfully used in treatment of moderate to severe COVID-19. It concludes that corticosteroids can reduce the risk of death in the most ill patients by up to 20%.

The remaining two papers are on research by teams working in France and Brazil which also support the use of steroids in critically ill patients with COVID-19.

Professor Jonathan Van-Tam, Deputy Chief Medical Officer said: 

“These findings offer further evidence that corticosteroids can be an important part of COVID-19 treatment for severe patients.

“Both the REMAP-CAP and the Bristol University papers show the important work that has been done here in the UK by researchers in making further major contributions towards the international evidence. It is impressive to see so many UK participants willing to take part in studies, and able to volunteer due to the rapid recruitment response of the NIHR’s Clinical Research Network. Research such as this will make the difference in controlling this virus.”

REMAP-CAP

REMAP-CAP (A Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia) is a nationally prioritised adaptive platform study investigating community-acquired pneumonia (CAP) a syndrome where people develop an acute infection of the lungs before being admitted to hospital. Bacterial and viral infections – like COVID-19 - are responsible for the vast majority of CAP. 

The study is being carried out at more than 246 sites across 15 countries, including 143 hospitals in the UK. Across the globe a total of 1,471 patients have been randomised into the study and 852 of those participants are COVID-19 patients. NIHR’s Clinical Research Network (CRN) recruited 520 COVID-19 participants. Patients receive one intervention in each of one or more categories of treatment (also called domains) these are: antibiotics, antivirals, steroids and convalescent plasma.

Today’s results from REMAP-CAP show that the steroid hydrocortisone led to improved survival rates and less need for intensive care support, including mechanical ventilation and blood pressure support, for seriously ill patients with COVID-19. However, the trial was stopped early, precluding definitive conclusions. 

384 patients were randomised for this part of the trial, with 137 receiving a seven-day fixed dose of hydrocortisone, 146 a shock dependent dose of hydrocortisone and 101 receiving none. This resulted in 93% and 80% probabilities of superiority for the fixed dose and the shock dependent doses respectively, with regard to the odds of improvement in organ support-free days within 21 days.

Anthony Gordon, Professor of Anaesthesia and Critical Care at Imperial College London,  and the study’s Chief Investigator, said: “The UK has been able to deliver so well in this study because of the joined up research processes that we have in this country. The NIHR provides infrastructure support to ensure research can be delivered efficiently throughout the whole NHS. This system is the envy of our international colleagues.”

Meta-analysis

The meta analysis looked at mortality over a 28-day period after the start of treatment. It showed that corticosteroids led to an estimated 20 per cent reduction in the risk of death. This is equivalent to around 68 per cent of patients surviving after treatment with corticosteroids, compared to around 60 per cent surviving in the absence of them. 

The seven RCTs recruited 1,703 critically ill patients in total, spanning five continents and including some of the countries hardest hit by coronavirus such as China, Brazil, Spain, the UK and the USA.

There was evidence of benefit from corticosteroids regardless of whether patients were receiving invasive mechanical ventilation at the time they started treatment. The benefit appeared greater among patients who were not so sick that they needed medicine to support their blood pressure, although the results were not definitive in this regard. The effect of corticosteroids appeared similar regardless of age, sex or how long patients had been ill.

Jonathan Sterne, Professor of Medical Statistics and Epidemiology at Bristol University, and Deputy Director of Bristol BRC, said: “Our review is good news in the effort to treat COVID-19, and provides important new information that builds on the findings of the RECOVERY trial.”

NHS chief executive Sir Simon Stevens said: “One of the distinctive benefits of having our NHS is that we've been able to mobilise quickly and at scale to help researchers test and develop proven coronavirus treatments. Just as we did with dexamethasone, the NHS will now take immediate action to ensure that patients who could benefit from treatment with hydrocortisone do so, adding a further weapon in the armoury in the worldwide fight against COVID-19.”

More information on the papers are available below: