Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts

N Engl J Med. 2020 Jul 23;383(4):309-320. doi: 10.1056/NEJMoa1915341. Epub 2020 Jul 8.


Background: Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear.

Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed.

Results: A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out.

Conclusions: Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Dibenzothiepins
  • Disease Transmission, Infectious / prevention & control*
  • Double-Blind Method
  • Endonucleases / antagonists & inhibitors
  • Family
  • Female
  • Humans
  • Influenza A virus* / genetics
  • Influenza A virus* / isolation & purification
  • Influenza, Human / prevention & control*
  • Influenza, Human / transmission
  • Influenza, Human / virology
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Morpholines
  • Oxazines / administration & dosage
  • Oxazines / adverse effects
  • Oxazines / therapeutic use*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Pyridones
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiepins / administration & dosage
  • Thiepins / adverse effects
  • Thiepins / therapeutic use*
  • Triazines / administration & dosage
  • Triazines / adverse effects
  • Triazines / therapeutic use*


  • Antiviral Agents
  • Dibenzothiepins
  • Morpholines
  • Oxazines
  • Pyridines
  • Pyridones
  • Thiepins
  • Triazines
  • baloxavir
  • Endonucleases

Associated data

  • JapicCTI/JapicCTI-184180