Nirmatrelvir/ritonavir (Paxlovid) reduces risk of hospitalization in at-risk outpatients (EPIC-HR)

Reference

National Institutes of Health. The COVID-19 treatment guidelines panel's statement on therapies for high-risk, nonhospitalized patients with mild to moderate covid-19. Published online 2022 Jan 19. https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-therapies-for-high-risk-nonhospitalized-patients/

Synopsis

Although the full results of this trial have not been peer-reviewed or even published, they are reported in the FDA package insert as well as in an NIH guideline. Nirmatrelvir is a protease inhibitor; its potency is increased by combining it with ritonavir. The researchers identified adults with confirmed COVID-19, symptom onset within the past 5 days, and either at least 60 years of age or a comorbidity that increases the risk of hospitalization and death. Patients with a history of COVID-19 infection or who were vaccinated were excluded. A total of 2246 participants were randomized to nirmatrelvir 300 mg/ritonavir 100 mg or matching placebo every 12 hours for 5 days. Their mean age was 46 years, two thirds had symptoms for 3 days or less, and the primary outcome was the likelihood of hospitalization or death due to COVID-19 within 28 days. This outcome was calculated for several modified intention-to-treat populations. In patients with 5 or fewer days of symptoms who didn’t or weren’t expected to get a COVID-19–specific monoclonal antibody (n = 2085) the primary outcome occurred significantly less often in the treatment group (0.8% vs 6.3%; P < .001; number needed to treat [NNT] = 18). The secondary outcome of all-cause mortality was also less likely in the treatment group (0.0% vs 1.1%; P = .001; NNT = 91). When analysis was limited to those with symptom onset in the past 3 days (n = 1379), results were similar (0.72% vs 6.45%; P < .001; NNT = 17). Most patients were infected with the delta variant, so the drug's efficacy in vaccinated persons and with the omicron variant is not known. Dosage adjustment is needed for patients with moderate or worse renal impairment. Because nirmatrelvir/ritonavir is a CYP3a inhibitor, there is a fairly large number of other drugs that should be withheld or their dose adjusted during administration, most notably other protease inhibitors and anti-HIV drugs, macrolides, calcium channel blockers, and statins. Otherwise, nirmatrelvir/ritonavir was well tolerated with few adverse events.