Although more than 1,000 clinical trials are testing treatment options for COVID-19, few have provided clear-cut results as yet. An adaptive platform trial known as RECOVERY, looking at multiple different treatments in parallel in hospitalized COVID-19 patients in the UK, has now given a verdict on three potential therapies. In a first positive result, the anti-inflammatory drug dexamethasone improves outcomes in patients with severe disease.
As of the end of June, the trial had recruited more than 11,500 patients onto various treatments including usual care. In an analysis of dexamethasone, researchers looked at outcomes from more than 2,100 patients who were treated with the steroid, compared with more than 4,300 patients on usual care. Overall, 21.6% of patients on dexamethasone died within 28 days, compared with 24.6% of patients on usual care, the investigators reported in a press release in June and in a preprint medRxiv article. Efficacy was most pronounced in ventilated patients, in which treatment reduced deaths by one third, and in patients who required oxygen, in which treatment reduced deaths by one fifth. Treatment did not reduce mortality in patients with milder disease, who were not on respiratory support.
“It is likely that the beneficial effect of corticosteroids in severe viral respiratory infections is dependent on using the right dose, at the right time, in the right patient. High doses may be more harmful than helpful, as may corticosteroid treatment given at a time when control of viral replication is paramount and inflammation is minimal,” the investigators wrote.
Increasing evidence suggests patient immune status may be important for COVID-19 therapeutics. Several immune-boosting agents are under clinical evaluation in patients whose immune systems may need help fending off infection.
Shortly after the disclosure of this landmark result, the RECOVERY trial reported that the HIV protease inhibitors lopinavir and ritonavir do not improve outcomes. Nearly 1,600 COVID-19 patients received lopinavir plus ritonavir, and their outcomes were compared with nearly 3,400 patients on usual care. On treatment, 28-day mortality was 22.1%, compared with 21.3% in the control arm, the investigators reported. These results were consistent across patient subgroups.
The RECOVERY trial has also found that hydroxychloroquine does not improve COVID-19 outcomes in hospitalized patients.
The WHO’s Solidarity trial, an international platform trial, subsequently also discontinued its exploration of lopinavir plus ritonavir, and of hydroxychloroquine, on the basis of interim and other results showing little or no evidence of reduction in mortality with these agents.
The RECOVERY trial is ongoing, now testing the antibiotic azithromycin, the IL-6-targeted anti-inflammatory therapy tocilizumab and convalescent plasma.
Nature Reviews Drug Discovery 19, 501 (2020)