To evaluate the efficacy of ensitrelvir in preventing symptomatic COVID-19 in household contacts exposed to SARS-CoV-2.
Approach:
Trial Design: A double-blind, randomized, placebo-controlled trial (SCORPIO-PEP) enrolling household contacts aged 12 years or older across multiple countries.
Participants: 1,030 participants received ensitrelvir and 1,011 received placebo, with enrollment within 72 hours of symptom onset in the index patient.
Treatment Regimen: Participants received ensitrelvir 375 mg on day 1, followed by 125 mg daily on days 2-5.
Primary Endpoint: COVID-19 by day 10, defined as laboratory-confirmed positivity plus at least one COVID-19 symptom lasting 48 hours.
Key Findings:
COVID-19 developed by day 10 in 3% of ensitrelvir recipients vs 9% of placebo recipients (risk ratio 0.33, P < .001).
67% relative risk reduction and an absolute risk reduction of 6.1 percentage points.
In the intention-to-treat population, COVID-19 developed in 4% of ensitrelvir vs 10% of placebo (risk ratio 0.43, P < .001).
Among participants with risk factors for severe illness, COVID-19 developed in 9 of 382 ensitrelvir recipients vs 37 of 374 placebo recipients.
Adverse events occurred in 15% of ensitrelvir recipients and 16% of placebo recipients, with no COVID-19-related hospitalizations or deaths.
Interpretation:
Limitations:
High immunity in the study population may limit generalizability.
Lack of data on household size, masking, and public health measures.
Exclusion of pregnant patients and those with recent SARS-CoV-2 infection or vaccination.
