Randomized Controlled Trial
Study population and setting
This study was conducted among hospitalized adults in China with COVID-19 and “severe” disease, defined by O2 saturation of ≤ 94% or PaO2:FiO2 ≤ 300 mm Hg. An open-label, individually randomized, controlled trial conducted from January 18, 2020, through February 3, 2020. 199 patients were included– 99 were assigned to receive lopinavir-ritonavir, and 100 were assigned to the standard of care (comprised of any of the following as necessary: supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO)). The primary outcomes were time to clinical improvement and mortality assessed by 28 days following enrollment.
Summary of Main Findings
The median interval time between symptom onset and randomization was 13 days (IQR:11 to 16 days).Treatment with lopinavir–ritonavir was not associated with a difference in the time to clinical improvement as compared to the standard of care (hazard ratio, 1.31; 95% CI: 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard ofcare group (19.2% vs. 25.0%; difference, −5.8%; 95% CI, −17.3 to 5.7). Detection of viral RNA at several time points did not differ between the groups. Lopinavir-ritonavir was stopped early in 14% of patients due to adverse events.
A trial conducted under emergency conditions providing some of the first randomized data on treatment for COVID-19.
Patients received therapy well into their disease course (average of 13 days), a larger trial targeting patients earlier may be justifiable. Among 99 patients assigned to lopinavir-ritonavir, 5 did not receive the therapy due to either death or refusal of administration by the attending physician. The study was neither blinded nor placebo-controlled. The study sample size was modest, and the study underpowered to detect more modest, yet still clinically relevant, effect sizes.
This is the first peer reviewed, published randomized trial of lopinavir-ritonavir for the treatment of SARS-Cov-2.