tetano
Editor, Senior Moderator
N Engl J Med
. 2026 May 14;394(19):1905-1915.
doi: 10.1056/NEJMoa2509306.
Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts
Frederick G Hayden[SUP] 1 [/SUP], Masaharu Shinkai[SUP] 2 [/SUP], Tristan W Clark[SUP] 3 [/SUP], Anne F Luetkemeyer[SUP] 4 [/SUP], Paul E Sax[SUP] 5 [/SUP], William P Hanage[SUP] 6 [/SUP], Kelly A Gebo[SUP] 7 [/SUP], Hideyuki Ikematsu[SUP] 8 [/SUP], Koichi Izumikawa[SUP] 9 [/SUP], Akimasa Fukushi[SUP] 10 [/SUP], Safwan Kezbor[SUP] 11 [/SUP], Hiroki Sakaguchi[SUP] 10 [/SUP], Stuart Lacey[SUP] 12 [/SUP], Genki Ichihashi[SUP] 10 [/SUP], Norio Ohmagari[SUP] 13 [/SUP], Takeki Uehara[SUP] 10 [/SUP]; SCORPIO-PEP Study Team
Collaborators, Affiliations
Background: Ensitrelvir, an oral inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease, is approved in Japan for the treatment of mild-to-moderate coronavirus disease 2019 (Covid-19). Previously, no antiviral agents were approved for postexposure prophylaxis in household contacts of patients with Covid-19.
Methods: In this double-blind, randomized, placebo-controlled trial, we randomly assigned persons who were SARS-CoV-2-negative on local diagnostic testing but were household contacts of a patient with Covid-19 (the index patient) to receive either ensitrelvir (375 mg on day 1 and 125 mg daily on days 2 through 5) or placebo within 72 hours after symptom onset in the index patient. The primary end point was Covid-19 (defined by a central laboratory-confirmed positive reverse-transcriptase-polymerase-chain-reaction assay and the presence of ≥1 of 14 prespecified Covid-19 symptoms lasting ≥48 hours) by day 10 in a household contact in the modified intention-to-treat population (all the participants who underwent randomization, had a central laboratory-confirmed negative RT-PCR test for SARS-CoV-2 at baseline, and received at least one dose of the trial drug or placebo).
Results: The modified intention-to-treat population included 1030 participants in the ensitrelvir group and 1011 in the placebo group. The mean age of the participants was 42.4 years; 71.1% had undergone randomization within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. The incidence of Covid-19 was lower in the ensitrelvir group than in the placebo group (2.9% vs. 9.0%; risk ratio, 0.33; 95% confidence interval [CI], 0.22 to 0.49; P<0.001). The incidence of adverse events during the trial was similar in the two groups (15.1% in the ensitrelvir group and 15.5% in the placebo group), as was the incidence of serious adverse events (0.2% in each group). No Covid-19-related hospitalizations or deaths were reported.
Conclusions: Ensitrelvir administered to household contacts of a patient with Covid-19 within 72 hours after symptom onset in the index patient was effective in preventing Covid-19 in the contacts. (Funded by Shionogi; SCORPIO-PEP Japan Registry for Clinical Trials number, jRCT2031230124; ClinicalTrials.gov number, NCT05897541.).
. 2026 May 14;394(19):1905-1915.
doi: 10.1056/NEJMoa2509306.
Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts
Frederick G Hayden[SUP] 1 [/SUP], Masaharu Shinkai[SUP] 2 [/SUP], Tristan W Clark[SUP] 3 [/SUP], Anne F Luetkemeyer[SUP] 4 [/SUP], Paul E Sax[SUP] 5 [/SUP], William P Hanage[SUP] 6 [/SUP], Kelly A Gebo[SUP] 7 [/SUP], Hideyuki Ikematsu[SUP] 8 [/SUP], Koichi Izumikawa[SUP] 9 [/SUP], Akimasa Fukushi[SUP] 10 [/SUP], Safwan Kezbor[SUP] 11 [/SUP], Hiroki Sakaguchi[SUP] 10 [/SUP], Stuart Lacey[SUP] 12 [/SUP], Genki Ichihashi[SUP] 10 [/SUP], Norio Ohmagari[SUP] 13 [/SUP], Takeki Uehara[SUP] 10 [/SUP]; SCORPIO-PEP Study Team
Collaborators, Affiliations
- PMID: 42127390
- DOI: 10.1056/NEJMoa2509306
Background: Ensitrelvir, an oral inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease, is approved in Japan for the treatment of mild-to-moderate coronavirus disease 2019 (Covid-19). Previously, no antiviral agents were approved for postexposure prophylaxis in household contacts of patients with Covid-19.
Methods: In this double-blind, randomized, placebo-controlled trial, we randomly assigned persons who were SARS-CoV-2-negative on local diagnostic testing but were household contacts of a patient with Covid-19 (the index patient) to receive either ensitrelvir (375 mg on day 1 and 125 mg daily on days 2 through 5) or placebo within 72 hours after symptom onset in the index patient. The primary end point was Covid-19 (defined by a central laboratory-confirmed positive reverse-transcriptase-polymerase-chain-reaction assay and the presence of ≥1 of 14 prespecified Covid-19 symptoms lasting ≥48 hours) by day 10 in a household contact in the modified intention-to-treat population (all the participants who underwent randomization, had a central laboratory-confirmed negative RT-PCR test for SARS-CoV-2 at baseline, and received at least one dose of the trial drug or placebo).
Results: The modified intention-to-treat population included 1030 participants in the ensitrelvir group and 1011 in the placebo group. The mean age of the participants was 42.4 years; 71.1% had undergone randomization within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. The incidence of Covid-19 was lower in the ensitrelvir group than in the placebo group (2.9% vs. 9.0%; risk ratio, 0.33; 95% confidence interval [CI], 0.22 to 0.49; P<0.001). The incidence of adverse events during the trial was similar in the two groups (15.1% in the ensitrelvir group and 15.5% in the placebo group), as was the incidence of serious adverse events (0.2% in each group). No Covid-19-related hospitalizations or deaths were reported.
Conclusions: Ensitrelvir administered to household contacts of a patient with Covid-19 within 72 hours after symptom onset in the index patient was effective in preventing Covid-19 in the contacts. (Funded by Shionogi; SCORPIO-PEP Japan Registry for Clinical Trials number, jRCT2031230124; ClinicalTrials.gov number, NCT05897541.).