A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

 

By Amy Orciari Herman

Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, DFASAM

Treatment with lopinavir–ritonavir did not add value beyond standard care in severely ill patients hospitalized with novel coronavirus disease (COVID-19). Findings from the open-label, randomized trial appear in the New England Journal of Medicine.

Roughly 200 adults in China hospitalized with COVID-19 and oxygen saturation of 94% or lower were assigned to lopinavir–ritonavir twice daily for 14 days plus standard care, or standard care alone. The primary outcome — time to clinical improvement — did not differ between the groups (median, 16 days). Mortality at 28 days was numerically lower with lopinavir–ritonavir, but the between-groups difference did not reach statistical significance (19% with lopinavir–ritonavir, 25% with standard care alone)

A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.

CONCLUSIONS

In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308. opens in new tab.

Bin Cao, M.D., Yeming Wang, M.D., Danning Wen, M.D., Wen Liu, M.S., Jingli Wang, M.D., Guohui Fan, M.S., Lianguo Ruan, M.D., Bin Song, M.D., Yanping Cai, M.D., Ming Wei, M.D., Xingwang Li, M.D., Jiaan Xia, M.D., et al.