“Dexamethasone is the first drug to be shown to improve survival in COVID-19. This is an extremely welcome result."
Treatment with a low-dose of the commonly used steroid dexamethasone has shown benefit in treating patients with coronavirus disease 2019 (COVID-19) who required respiratory intervention, according to findings from 1 arm of the RECOVERY trial in the United Kingdom (UK).1
Findings from the cohort were announced in a press release from the University of Oxford, but the investigators are working quickly to publish the full results.
If these findings are confirmed, they would be significant given the low cost and accessibility of dexamethasone, which is frequently used in anticancer regimens, allowing for immediate benefit in patients with COVID-19.
“Dexamethasone is the first drug to be shown to improve survival in COVID-19. This is an extremely welcome result. The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients,” Peter Horby, MD, PhD, professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and 1 of the chief investigators for the trial, said in a statement. “Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.”
The RECOVERY trial is an ongoing large, randomized, controlled clinical trial in the UK that is exploring various potential treatment options for patients hospitalized for COVID-19, including lopinavir/ritonavir, hydroxychloroquine, azithromycin, tocilizumab, and convalescent plasma from patients who have recovered from COVID-19, and low-dose dexamethasone. The trial was initiated in March 2020, and so far, over 11,500 patients have been enrolled in the study from more than 175 hospitals.
In the dexamethasone arm, 2104 patients were randomized to received either oral or intravenous dexamethasone 6 mg per day for 10 days. Outcomes from this arm were compared with 4321 patients randomized to receive usual care alone.
Enrollment in the dexamethasone arm was halted on June 8 as the steering committee decided that enough patients had been enrolled in the arm to establish whether or not the drug provided meaningful benefit.
Dexamethasone reduced the risk of death by 35% in ventilated patients (rate ratio, 0.65; 95% CI, 0.48-0.88; P = .0003) and by 20% in patients receiving oxygen only (rate ratio, 0.80; 0.67-0.96; P = .0021). Patients who do not require respiratory support, however, did not show a benefit from dexamethasone treatment (rate ratio, 1.22; 95% CI, 0.86-1.75; P = .14). This amounted to 1 of about 8 ventilated patient deaths being prevented or 1 in about 25 deaths prevented in patients requiring oxygen.
Patients who received usual alone showed a 41% rate of mortality at day 28, 25% mortality rate for patients who required oxygen alone, and a 13% rate in patients who did not require respiratory intervention.
Treatment with dexamethasone reduced the rate of 28-day mortality by 17% (rate ratio, 0.83; 95% CI, 0.74-0.92; P =.0007). A highly significant trend for benefit was seen among patients requiring ventilation (P <.001).
“This is tremendous news today from the Recovery trial showing that dexamethasone is the first drug to reduce mortality from COVID-19. It is particularly exciting as this is an inexpensive widely available medicine,” said Sir Patrick Vallance, FRS, FMedSci, FRCP, the chief scientific adviser to the UK government, in a statement. “This is a ground-breaking development in our fight against the disease, and the speed at which researchers have progressed finding an effective treatment is truly remarkable. It shows the importance of doing high quality clinical trials and basing decisions on the results of those trials.”
“Since the appearance of COVID-19 6 months ago, the search has been on for treatments that can improve survival, particularly in the sickest patients. These preliminary results from the RECOVERY trial are very clear—dexamethasone reduces the risk of death among patients with severe respiratory complications. COVID-19 is a global disease—it is fantastic that the first treatment demonstrated to reduce mortality is one that is instantly available and affordable worldwide,” Martin Landray, MB ChB, PhD, professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, one of the chief investigators, said in a statement.
Following the news, the World Health Organization (WHO) noted that they welcomed the preliminary results.2
“This is great news and I congratulate the Government of the UK, the University of Oxford, and the many hospitals and patients in the UK who have contributed to this lifesaving scientific breakthrough,” said Tedros Adhanom Ghebreyesus, PhD, MSc, director-general, WHO, in a statement.
Additionally, the UK government approved the use of dexamethasone for use in the treatment of patients hospitalized with COVID-19 requiring oxygen or ventilators.3
In further findings from the RECOVERY trial, an independent data monitoring committee has affirmed that the hydroxychloroquine arm has shown no significant benefit in patients hospitalized with COVID-19.4
A total of 1542 patients were randomized to the hydroxychloroquine arm. The rate of 28-day mortality was 25.7% in the hydroxychloroquine arm compared with 23.5% with usual care (hazard ratio, 1.11; 95% CI, 0.98-1.26; P = .10). No evidence of benefit was seen in terms of hospital stay duration or other outcomes with hydroxychloroquine.