lopinavir/ritonavir (n=99) vs. standard of care (n=100)
randomized controlled trial
Lopinavir–ritonavir
Lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care.
Standard care
Standard care alone.
Both groups received standard care: supplemental oxygen,noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO).
COVID-19 severe or critically
Male and nonpregnant female patients 18 years of age or older were eligible if they had a diagnostic specimen that was positive on RT-PCR, had pneumonia confirmed by chest imaging, and had an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2)(Pao2:Fio2) at or below 300 mg Hg.
Open-label.
Single center, Jin Yin-Tan Hospital, Wuhan, Hubei Province, China.
The seven-category ordinal scale consisted of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized,but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4,hospitalized, requiring supplemental oxygen; 5,hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7, death.
lopinavir/ritonavir (n=268) vs. standard of care (n=377)
randomized controlled trial
Lopinavir/ritonavir
400 mg of lopinavir and 100 mg of ritonavir every 12h for 5 days minimum, up to a maximum of 14 days or until ICU discharge whichever occurred first. Patients with a gastric tube who were unable to swallow tablets, lopinavir-ritonavir (at the same dose) was administered as a 5-ml suspension every 12h or alternatively as two dissolved tablets or four crushed tablets (double dose).
Standard of care
No antiviral treatment.
COVID-19 severe or critically
≥18 years old, admitted with suspected or confrmed COVID-19, and were receiving respiratory or cardiovascular organ failure support in an intensive care unit (ICU). Organ support included the provision of invasive mechanical ventilation, noninvasive mechanical ventilation, high-fow nasal cannulae with a fow rate of at least 30 L per minute and a fractionalinspired oxygen concentration of 0.4 or higher, or the infusion of vasopressor or inotropes for shock.
Open-label.
99 sites across 8 countries.
In the register PE was: all-cause mortality (day 90); days alive and not receiving organ support in ICU (day 21).
Enrollment into the lopinavir-ritonavir arm was halted on November 19, 2020, after reaching the prespecifed futility threshold.
