LOTUS China
Trial question
What is the effect of lopinavir-ritonavir in adults hospitalized with severe COVID-19?
Study design
Single center
Open label
RCT
Population
Characteristics of study participants
40.0% female
60.0% male
N = 199
199 patients (79 female, 120 male).
Inclusion criteria: hospitalized adult patients with confirmed COVID-19 infection.
Key exclusion criteria: known allergy or hypersensitivity to lopinavir-ritonavir; known severe liver disease; use of medications that are contraindicated with lopinavir-ritonavir and that could not be replaced or stopped during the trial period; pregnancy or lactation; or known HIV infection.
Interventions
N=99 lopinavir-ritonavir (400 mg and 100 mg twice a day for 14 days plus standard care for 14 days).
N=100 standard care (standard care alone for 14 days).
Primary outcome
Time to clinical improvement
16 days
16 days
16.0 days
12.0 days
8.0 days
4.0 days
0.0 days
Lopinavir-ritonavir
Standard
care
No significant
difference ↔
No significant difference in time to clinical improvement (16 days vs. 16 days; HR 1.31, 95% CI 0.95 to 1.85).
Secondary outcomes
No significant difference in the rate of death by day 28 (19.2% vs. 25%).
Borderline significant decrease in length of ICU stay (6 days vs. 11 days; AD -5 days, 95% CI -9 to 0).
No significant difference in duration of invasive mechanical ventilation (4 days vs. 5 days; AD -1 days, 95% CI -4 to 2).
Safety outcomes
No significant difference in adverse events or shock.
Significant differences in gastrointestinal adverse events, which were more common in the placebo group - and serious adverse events, which were more common in the standard care group.
Conclusion
In hospitalized adult patients with confirmed COVID-19 infection, lopinavir-ritonavir was not superior to standard care with respect to time to clinical improvement.
Reference
Bin Cao, Yeming Wang, Danning Wen et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799.
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