As the number of confirmed cases of coronavirus disease 19 (COVID-19) continues to rise, researchers work to discover new treatments and vaccines. Currently, there are no specific treatments for COVID-19.

However, in December 2019, with less than 500 confirmed COVID-19 cases worldwide, a small trial was initiated at the Jin-Tan Hospital to investigate whether anti-viral drugs, such as lopinavir-ritonavir, commonly used to treat human immunodeficiency virus (HIV) infection would relieve the symptoms of COVID-19.

In addition to other medications, protease inhibitors lopinavir and ritonavir are used to treat HIV by decreasing the amount of HIV in the blood. When lopinavir and ritonavir are taken together, ritonavir also helps to increase the amount of lopinavir in the body so that the medication will have a greater effect.

In this randomized, open-label trial, 199 patients (median age, 58 years) were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days in addition to standard care or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.

Results showed that lopinavir-ritonavir treatment added to standard supportive care was not associated with clinical improvement or mortality in seriously ill patients with COVID-19 different from that associated with standard care alone. However, in the modified intention-to-treat analysis, which excluded three patients with early death, the between-group difference in the median time to clinical improvement (median, 15 days vs 16 days) was significant.

Of note, the overall mortality in this trial (22.1%) was substantially higher than the 11% to 14.5% mortality reported in initial descriptive studies of hospitalized patients with COVID-19, indicating that a severely ill population had been enrolled.

The findings from this study will be part of the new Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial, which provides a platform to evaluate about 20 treatments that are currently thought to have potential for treating COVID-19. The chief investigator in the RECOVERY trial will be Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine at the University of Oxford, who was also part of the small trial in Wuhan. In contrast to the usual six to nine months for a trial to get started, the RECOVERY trial enrolled the first patient in nine days.

Taking a cue from trials in China that are kept simple, RECOVERY is using a very short protocol and minimal burden on hospital staff who are currently overwhelmed by ensuring simple data collection. The RECOVERY trial is classified as an Urgent Public Health Research Study.

Another trial is currently recruiting in the United Kingdom, Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP), evaluating the impact of treatment in severely ill patients. The researchers in both the RECOVERY and REMAP-CAP trials will be working together to learn as much as possible for each other.