Positive prospects for dexamethasone in COVID-19 patients

The University of Oxford announces that dexamethasone, a low-cost drug, reduces by up to one third the deaths of hospitalized COVID-19 patients with serious respiratory complications.

Encouraging first results of the RECOVERY study

The University of Oxford announces that dexamethasone, a low-cost drug, reduces by up to one third the deaths of hospitalized COVID-19 patients with serious respiratory complications. The study and full research data will soon be made available.

In March 2020, the RECOVERY project (Randomized Evaluation of COVid-19 thERapY) a randomized clinical trial was prepared to test a range of potential therapeutic treatments for COVID-19, including low-dose dexamethasone (a steroidal anti-inflammatory drug). In the UK, the NHS (National Health Service) has enrolled over 11,500 patients from 175 hospitals. On 8 June, the enrollment of patients in the study arm investigating the efficacy of dexamethasone was discontinued, as it was considered that there were already enough patients to determine whether or not the drug had a significant benefit.

A total of 2,104 patients were randomized to be treated with dexamethasone 6 mg once daily (by mouth or intravenously) for ten days and were compared with 4,321 patients receiving standard treatment. Among patients who received only standard care, mortality at 28 days was higher among those who were mechanically ventilated (41%), intermediate in those patients receiving oxygen therapy (25%), and lower among those who did not require respiratory support (13%).

Dexamethasone reduced deaths by 1/3 in artificially ventilated patients (rate ratio 0.65 [95% confidence interval from 0.48 to 0.88]; p=0.0003) and by 1/5 in patients on oxygen therapy alone (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among patients who did not need respiratory support (1.22 [0.86 to 1.75]; p=0.14).

One of the trial leaders, Peter Horby, Professor of Emerging Infectious Diseases at the Department of Medicine in Nuffield, University of Oxford, said: "Dexamethasone is the first drug that has been shown to increase the survival of COVID-19 patients. This is a result that fills us with joy. The benefit in terms of survival is clear and greater in patients with severe conditions, who require oxygen support. Dexamethasone should now become the standard of care in these patients. Dexamethasone is inexpensive, available, and can be used immediately to save lives around the world”.

Reactions from experts

Duncan Young, Professor of Intensive Care Medicine at Oxford University, said: "The results of the RECOVERY study on dexamethasone show improved survival at 28 days in COVID-19 patients with disease severe enough to require supplemental oxygen or artificial ventilation. The results are very robust for the large number of patients recruited into the study. The drug prevented 1 in 8 deaths in ventilated patients and 1 in 25 deaths in oxygen therapy patients. Although this seems a relatively modest effect on outcome, for ventilated patients the NNT (number needed to treat) of 8 is the best result of almost all other interventions studied in these patients. It will be interesting to see whether the improvement in survival with dexamethasone persists unchanged beyond 28 days, and whether the drug mitigates the severity of the disease or reduces long-term complications in survivors”.

Dr. Penny Ward, Professor of Pharmaceutical Medicine at King's College London and Chair of the Education and Standards Committee of the Faculty of Pharmaceutical Medicine, said: "Finally, good news for COVID-19 patients with respiratory failure who need ventilatory support in intensive care, the group where antiviral therapy with remdesivir has been less successful and where the mortality rate is higher. Clinicians will need to see detailed results of the study, particularly those of patients who do not require oxygen therapy/fan support, as the breakdown of outcomes by stage of disease suggests that the timing of initiation of steroid use may be relevant to use the treatment in the most efficient way. That said, for critical patients, there is good news today”.

Dr. Ayfer Ali, assistant at Warwick Business School, said: "The results seem to be extremely encouraging and this will now be one of the most important tools against COVID-19 in seriously ill patients. Dexamethasone is cheap and easily available in tablet form. As such, it can be used much more easily than the antiviral drug remdesivir, which has to be administered in hospital as an infusion. This would also be the first drug that actually shows a reduction in mortality rates, rather than a simple reduction in the duration of the disease”. Dr. added that “now we have to wait for the full results to be peer-reviewed and remember that it is not a cure for everyone, just another tool. But this shows the potential of re-adapting drugs. The important thing is to determine which patients should take this drug, since presumably not everyone would need it, and what would be the most appropriate time to start treatment in COVID-19 positive patients, since clearly this drug should not be administered as a preventive measure".

Professor Robin Ferner, Honorary Professor of Clinical Pharmacology at the University of Birmingham and Honorary Medical Advisor at City Hospital in Birmingham, said: "The important findings of the Oxford group, based on a scientific study of over 6,000 NHS patients, show that dexamethasone - a common, widely used and inexpensive medicine - can save lives in seriously ill patients with COVID-19. It is not a treatment for mild symptoms. We hope that the data on which these findings are based will be published as soon as possible so that doctors can implement the treatment with confidence”.

Dr. Nick Cammack, COVID-19 Therapeutics Accelerator Lead, Wellcome Trust, said: "This is an important step forward: dexamethasone is the first and only drug that has made a significant difference in patient mortality for COVID-19. Finding effective treatments like this will transform the impact of the COVID-19 pandemic on lives and economies around the world. Dexamethasone must now be distributed and accessible to thousands of seriously ill patients worldwide. It is highly affordable, easy to make, can be scaled rapidly and requires low dosage. Any successful treatment against COVID-19 must be made available to all those who need it globally, regardless of their ability to pay for it. Having these results in such a short time is an incredible scientific achievement. The data will give researchers around the world a better understanding of why the drug is effective in these patients. This is extremely promising news and a significant step forward, but we still have a long way to go. To end this pandemic, we still need better diagnostics, effective treatment drugs and vaccines to prevent COVID-19”.

Sources:
1. Oxford University News Release. Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. University of Oxford. 16 June 2020
2. Expert reaction to the RECOVERY trial reporting that dexamethasone reduces death by up to one third in hospitalised COVID-19 patients with severe respiratory complications. Science Media Centre. June 16 2020

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