N Engl J Med

Paxlovid disappoints in COVID-19 post-exposure prophylaxis trial

July 19, 2024

Postexposure prophylaxis with nirmatrelvir–ritonavir for 5 or 10 days failed to significantly reduce risk of symptomatic SARS-CoV-2 infection.

• In the phase 2–3, double-blind EPIC-PEP trial, asymptomatic, rapid antigen test–negative adults who’d been exposed to a household contact with COVID-19 were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir–ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) q12h for 5 days or for 10 days or matching placebo for 5 or 10 days. Primary endpoint was development of symptomatic SARS-CoV-2 infection, confirmed on RT-PCR or rapid antigen testing through 14 days.
• Of 2,736 total participants, 921 were randomly assigned to the 5-day nirmatrelvir-ritonavir group, 917 to the 10-day nirmatrelvir-ritonavir group, and 898 to the placebo group. Rates of symptomatic, confirmed SARS-CoV-2 infection by day 14 were 2.6% in the 5-day nirmatrelvir-ritonavir group, 2.4% in the 10-day nirmatrelvir-ritonavir group, and 3.9% in the placebo group. The proportion who developed symptomatic, confirmed SARS-CoV-2 infection didn’t differ significantly among the 3 groups. Incidence of adverse events was similar across groups. Dysgeusia was most frequent, reported in 5.9% and 6.8% of the 5-day and 10-day nirmatrelvir-ritonavir groups, respectively, and in 0.7% of the placebo group.

Source:

Hammond J, at al. (2024, June 17). Thorax. Oral Nirmatrelvir-Ritonavir as Postexposure Prophylaxis for Covid-19. https://pubmed.ncbi.nlm.nih.gov/39018532/