As COVID-19 has infected more than 245,000 people and killed more than 10,000 as of last Friday afternoon, a cure or vaccine continues to elude researchers worldwide. Nonetheless, a recent study, in which Tigermed’s Central Lab participated, shares insights into the effects of lopinavir-ritonavir in hospitalized adult patients with severe Covid-19.
As a company we are proud to be a part of what the New England Journal of Medicine refers to as a ‘brave’ trial and to be able to have actively participated in the fight against COVID-19; no matter the difficulty.
New England Journal of Medicine’s editors commented on the trial:
“It is quite remarkable how quickly you were able to stand up this study a little over a week after the virus was identified.”
Reasoning behind the study
Although there are no specific therapeutic agents for coronavirus infections on the horizon yet, researchers are working tirelessly to find a cure and are looking into related diseases in history as well.
- Following the SARS-outbreak in 2003, lopinavir was identified to have in vitro inhibitory activity against SARS-CoV, the virus that causes SARS in humans.
- Ritonavir is combined with lopinavir to increase its plasma half-life through the inhibition of cytochrome P450.
- An open-label study published in 2004 suggested, by comparison with a historical control group that received only ribavirin, that the addition of lopinavir-ritonavir (400 mg and 100 mg, respectively) to ribavirin reduced the risk of adverse clinical outcomes (acute respiratory distress syndrome [ARDS] or death) as well as viral load among patients with SARS. However, the lack of randomization and a contemporary control group and the concomitant use of glucocorticoids and ribavirin in that study made the effect of lopinavir-ritonavir difficult to assess.
- Similarly, lopinavir has activity, both in vitro and in an animal model, against Middle East respiratory syndrome coronavirus (MERS-CoV), and case reports have suggested that the combination of lopinavir-ritonavir with ribavirin and interferon alfa resulted in virologic clearance and survival.
The study and patients
Of the 199 patients who were enrolled in the study and underwent randomization, 99 patients were assigned to receive lopinavir-ritonavir and 100 patients to standard care alone.
Full study randomization and treatment assignment:
In this randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, no benefit was observed with treatment beyond standard care.
However, these early data are a step forward in the sense that they aid us to make informed decisions in future studies of possible treatment of infection with SARS-CoV-2 and will help to determine whether combining lopinavir-ritonavir with other antiviral agents, might enhance antiviral effects and improve clinical outcomes.
Although these results may not be what healthcare professionals are eagerly anticipating, additional trials in patients like these help to confirm or exclude the possibility of a treatment benefit and hopefully precede a possible cure for COVID-19.
Read the full article in the New England Journal of Medicin here.