Research into critically ill patients with COVID-19, published today in JAMA, shows fewer patients died and less intensive care (ICU) support was required when patients received corticosteroids compared with usual treatment. And the effect was consistent for those receiving either hydrocortisone or dexamethasone.
One of these studies was the international multi-centre REMAP-CAP trial, which in New Zealand is coordinated by the Medical Research Institute of New Zealand and funded by the Health Research Council of New Zealand (HRC).
In April, the trial was awarded additional funding by the HRC and Ministry of Health to investigate a range of potential therapies for COVID-19 in critically ill patients, and has subsequently found that treatment with the steroid hydrocortisone had a high probability of reduced death and less time on organ support in ICU, especially in patients not yet requiring breathing support with a ventilator.
These findings and those of six other studies were combined in a prospective meta-analysis conducted by the World Health Organization (WHO) and are expected to change how doctors treat COVID-19 patients in the ICU.
Dr Colin McArthur, intensivist and researcher at Auckland City Hospital, who leads the REMAP-CAP trial in New Zealand and is a co-author of the WHO meta-analysis published today, says the seven randomised clinical trials showed similar results across patients receiving either hydrocortisone (tested in three trials), dexamethasone (tested in three trials), or methylprednisolone (tested in one trial).
In the analysis involving 1703 patients, the odds of death within 4 weeks was much lower among patients who received corticosteroids compared with those who received usual care or placebo. Of those randomised to corticosteroids there were 222 deaths and 456 survivors, compared to 425 deaths and 600 survivors of those randomised to usual care or placebo.
“That equates to over 20% fewer deaths,” says Dr McArthur, who adds that one extra patient would survive for every 11 treated with corticosteroids.
This evidence from these additional studies reinforces the results of the UK-based RECOVERY trial which published its findings into dexamethasone in July. As a result of the RECOVERY trial, many hospitals around the world adopted dexamethasone as part of their usual care for severely ill patients with COVID-19, and most ongoing clinical trials of corticosteroids paused recruitment – including those investigating hydrocortisone as a potential treatment.
Dr McArthur says the meta-analysis confirms that hydrocortisone is similarly effective as dexamethasone in treating critically ill patients with COVID-19.
“We’ve now confirmed that hydrocortisone is an acceptable alternative to dexamethasone. I don’t think there’s going to be any question now about corticosteroids being the standard of care.”
He says it’s important for clinicians to have options, especially if there are drug supply issues, and another advantage with both these treatments is that they are inexpensive.
Dr McArthur says that with the benefit of corticosteroids now established, going forward the REMAP-CAP trial will be testing a range of other treatments to further improve the survival rate from COVID-19. Convalescent plasma, anti-coagulation and anti-platelet treatments are planned to be added to the study in New Zealand soon.
Professor Sunny Collings, Chief Executive of the Health Research Council, says it’s imperative to support trials like REMAP-CAP that are playing a critical role in international efforts to answer life-saving questions during this pandemic.
“Thanks to RECOVERY, REMAP-CAP and the other trials in this meta-analysis, we now know that corticosteroids have an effect that’s consistent across multiple trials. This not only reinforces the role of dexamethasone in COVID-19 treatment but convincingly establishes hydrocortisone as another treatment option.”
Professor Richard Beasley, Director of the Medical Research Institute of New Zealand, says it is remarkable to have strong evidence of a therapy that saves lives within nine months of the disease first appearing.
“It is also a great achievement that New Zealand has been able to have a strong international leadership role in the clinical trials programme that has led to this evidence, based on the support of the Health Research Council and the Ministry of Health,” he says.
Professor Ian Town, Chief Science Advisor at the Ministry of Health, welcomes the findings which confirm the critical role that corticosteroids play in mitigating the impacts on lung function – “such a worrying feature of severe COVID-19 infection”.
“We have known for a long time that steroids can help damp down the pulmonary inflammation in a variety of acute situations, so it is very encouraging to see a strong evidence base for their use in COVID-19.”