The antiretroviral combination of lopinavir/ritonavir has no significant mortality benefit in hospitalised COVID-19 patients, preliminary results from the RECOVERY trial show.

The findings come after a routine review of emerging data by the independent Data Monitoring Committee led them to recommend that the chief investigators be unblinded to the results for the lopinavir-ritonavir arm.

Overall, 1596 patients were randomised to lopinavir-ritonavir compared with 3376 patients randomised to usual care alone. Of these patients, 4% required invasive mechanical ventilation when they entered the trial, 70% required oxygen alone, and 26% did not require any respiratory intervention.

There was no significant difference in the primary endpoint of 28-day mortality (22.1% lopinavir-ritonavir vs. 21.3% usual care; relative risk 1.04 [95% confidence interval 0.91-1.18]; p=0.58) and the results were consistent in different subgroups of patients.

There was also no evidence of beneficial effects on the risk of progression to mechanical ventilation or length of hospital stay.

The researchers noted that they could not make conclusions about the effectiveness in mechanically ventilated patients because of the difficulty in administering the drug to these patients.

A combination of lopinavir with ritonavir – registered for use in HIV – had previously shown promising activity against SARS and MERS coronaviruses.

Professor Peter Horby, University of Oxford, and Chief Investigator for the trial, said: “Today we release the third set of results from the RECOVERY trial. These preliminary results show that for patients hospitalised with COVID-19 and not on a ventilator, lopinavir-ritonavir is not an effective treatment.

In 100 days, the RECOVERY trial has provided results enabling change in global practice three times. This extraordinary national effort has shown that two drugs used to treat hospitalised COVID patients throughout the world, hydroxychloroquine and lopinavir-ritonavir, do not improve survival, whilst one drug that was not recommended, dexamethasone, saves lives.

The findings are yet to be peer reviewed or published in a journal.