A protocol for randomized, controlled study of baloxavir marboxil compared with oseltamivir in patients with influenza virus infection aged 75 years and older

Introduction: Early treatment with antiviral therapy is recommended for patients with severe influenza or those who are at high risk of influenza complications. Baloxavir marboxil is a cap-dependent endonuclease inhibitor approved for treatment of uncomplicated influenza in otherwise healthy adults and adolescents >12 years in the United States and for influenza infection in adults, adolescents ≥12 years, and in children <12 years weighing ≥10 kg in Japan. Analysis of the subgroup of patients ≥75 years in the CAPSTONE-2 trial suggests that the median time to improvement in influenza symptoms is numerically shorter in elderly patients treated with baloxavir or oseltamivir compared with placebo. The current study is designed to extend these findings and compare the efficacy and safety of baloxavir and oseltamivir in Japanese patients ≥75 years with acute influenza virus infection. Methods: In this open-label, multicenter, randomized, active-controlled trial, 100 Japanese patients ≥75 years with acute influenza virus infection will be randomly allocated (1:1) to receive a single oral dose of baloxavir 40 mg/80 mg (body weight–based) or twice-daily oral oseltamivir 75 mg for 5 days. At the time of allocation, patients will be stratified by their Influenza Symptom Severity Scale total scores (≤14, ≥15) on Day 1. The primary efficacy endpoint is the time to improvement of influenza symptoms, from the time of first administration of study drug to the time when the severity of each symptom is improved or absent for at least 21.5 hours in the intention-to-treat infected population (all randomized patients with an reverse-transcriptase polymerase chain reaction -confirmed influenza virus infection on Day 1 and who receive at least 1 dose of study drug). Safety will be assessed in all randomized patients who received at least 1 dose of study drug. Discussion: Because of the long life expectancy in Japan, the Japanese population presents a unique opportunity in which to investigate the efficacy and safety of antiviral drugs in patients ≥75 years with influenza. The outcomes from this trial will be clinically relevant for Japan and other developed countries that have rapidly aging societies who are at high risk of influenza-associated complications. Trial registration: jRCTs071200034