Intravenous remdesivir for 3 days reduces hospitalization in outpatients with symptomatic COVID-19

Reference

Gottlieb RL, Vaca CE, Paredes R, et al, for the GS-US-540-9012 (PINETREE) Investigators. Early remdesivir to prevent progression to severe covid-19 in outpatients. N Engl J Med 2021 [published online ahead of print, 2021 Dec 22]; doi:10.1056/NEJMoa2116846.

Synopsis

Remdesivir was among the first antiviral drugs found to provide some benefit for patients with COVID-19, albeit primarily in those who were hospitalized with moderate to severe disease. As a drug that inhibits viral replication, one might expect a benefit in the early phase of disease, as well. These investigators identified persons 12 years or older with risk factors for severe COVID-19 (vascular disease; diabetes mellitus; body mass index 30 or higher; immune compromise; active cancer; sickle cell disease; or chronic kidney, lung, or liver disease) and persons 60 years or older, regardless of whether they had risk factors. They all had symptom onset within the past 7 days and a positive molecular test result within 4 days of study entry. Patients expected to need oxygen or hospitalization were excluded, as were patients who had received a COVID-19 vaccine. The authors randomized patients to intravenous (IV) remdesivir 200 mg once on day 1 and 100 mg once daily on days 2 and 3, or matching placebo infusion. Although the trial had been expected to enroll 1264 patients, only 584 were ultimately randomized — the trial was stopped early due to increasing vaccination rates, the availability of alternate effective treatments such as monoclonal antibodies, and the declining incidence of COVID-19 in the spring of 2021. Groups were balanced at baseline with a mean age of 50 years, 30% aged 60 years or older, and the most common comorbidities being diabetes mellitus, obesity, and hypertension. At 28 days, the likelihood of hospitalization or death was significantly lower in the remdesivir group (0.7% vs 5.3%; P = .008; number needed to treat [NNT] = 22). No one in either group died within 28 days of randomization. The benefit was consistent across subgroups defined by age and comorbidities. The drug was well-tolerated.