Data From the RECOVERY Trial Do No Support Use of Lopinavir-Ritonavir for COVID-19

October 6, 2020

Lopinavir-ritonavir is not an effective treatment for patients admitted to hospital with coronavirus disease 2019 (COVID-19), according to findings from the Randomised Evaluation of Covid-19 Therapy (RECOVERY) trial, published in The Lancet.

Many clinical care guidelines have recommended lopinavir-ritonavir for the treatment of patients hospitalised with COVID-19. However, these guidelines should now be updated, said Martin Landray, MD, University of Oxford, Oxford, United Kingdom.

“Treatment of COVID-19 with the drug combination lopinavir–ritonavir has been recommended in many countries,” said Landray. “However, results from this trial show that it is not an effective treatment for patients admitted to hospital with COVID-19. Since our preliminary results were made public on June 29, 2020, the World Health Organization has halted lopinavir-ritonavir treatment groups involved in its SOLIDARITY trial and reported that their interim results are in line with those presented here.”

Between March 19, 2020, and June 29, 2020, a total of 1,616 patients were randomised to receive lopinavir-ritonavir while 3,424 patients received usual care alone. Those on lopinavir-ritonavir received oral lopinavir 400 mg/ritonavir 100 mg every 12 hours for 10 days or until discharge, if sooner. The primary outcome was 28-day all-cause mortality.

The 28-day all-cause mortality rate in the lopinavir-ritonavir arm was 23% compared with 22% among patients in the usual care arm.

The combination treatment did not reduce the length of patients’ hospital stay, with 69% of patients in the lopinavir-ritonavir arm leaving the hospital within 28 days, compared with 70% of patients in the usual care arm. Both groups had a median stay of 11 days.

Of the patients in the lopinavir-ritonavir arm, 10% required ventilator support compared with 9% of patients in the usual care arm.

Results were consistent across all patient subgroups, including age, sex, and ethnicity.

“Whilst it is disappointing that there was no significant benefit from lopinavir-ritonavir for patients in hospital, these findings have allowed us to focus our efforts on other promising treatments, and have informed the way in which individual patients are treated,” said Peter Horby, MD, University of Oxford.

The authors noted that few patients who had undergone intubation took part in the trial due to difficulties in giving oral treatment to patients who could not swallow, and so it is not possible to draw conclusions about the effectiveness of lopinavir-ritonavir for mechanically ventilated patients.

In an accompanying commentary, Bin Cao, MD, China-Japan Friendship Hospital, Beijing, Republic of China, and Frederick G. Hayden, University of Virginia School of Medicine, Charlottesville, Virginia, wrote: “Compared with the first randomised trial to investigate lopinavir-ritonavir in patients with COVID-19 by Cao and colleagues (including the authors of this Comment), the size of the lopinavir-ritonavir group in the RECOVERY trial was much larger and hence provides a more solid evidence base regarding possible lopinavir-ritonavir treatment effects. […] The findings of these 2 open-label studies support each other and conclude that lopinavir-ritonavir is not effective in improving outcomes for patients admitted to hospital with COVID-19.”

Reference: www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32013-4/fulltext

SOURCE: The Lancet