臨床研究等提出・公開システム

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

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

1

The original target number of subjects was set at 100 (50/group). However, this study was terminated with one enrollment as the achievement of target number of subjects was considered difficult due to reduction of the number of influenza patients probably because of infection control measures for COVID-19. The subject enrolled was 79-year-old male and had moderate headache, nasal stuffiness, muscle or joint pain, and mild cough. The influenza rapid diagnostic test of this subject was positive for influenza A. This subject was allocated to baloxavir marboxil group. As the influenza PCR test of baseline sample was negative, this subject was not applicable to major efficacy analysis set.

While the study began in November 2020 and the end of enrollment period was set April 2023, termination of this study was determined in September 2022. The enrolled subject provided with informed consent for this study participation received scheduled baloxavir marboxil treatment, and completed study in February 2021.

The subject treated with baloxavir marboxil had no adverse event.

The primary and secondary endpoints were not analyzed. The result of the enrolled subject was as follows: [Primary endpoint] Time to improvement of influenza symptoms: 5.92 hours [Secondary endpoint] - Time to alleviation of seven influenza symptoms (cough, sore throat, headache, nasal stuffiness, feeling hot or chills, muscle or joint pain, and a feeling of fatigue): 5.92 hours - Time to improvement in the four systemic symptoms (headache, feeling hot or chills, muscle or joint pain, and a feeling of fatigue): 5.92 hours - Time to improvement in the three respiratory symptoms (cough, nasal stuffiness, and sore throat): 5.92 hours - Time to return to pre-influenza health status: 270.92 hours

The original target number of subjects was set at 100 (50/group). However, this study was terminated with one enrollment as the achievement of target number of subjects was considered difficult due to reduction of the number of influenza patients probably because of infection control measures for COVID-19, and any planned analyses of endpoints were not conducted. The time to improvement of influenza symptoms for the subject was 5.92 hours, and no adverse event was observed.

Dec. 23, 2022

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs071200034

Mukae Hiroshi

Nagasaki University Hospital

1-7-1 Sakamoto Nagasaki-city Nagasaki ,Japan

hmukae@nagasaki-u.ac.jp

Takazono Takahiro

Nagasaki University Hospital

1-7-1 Sakamoto Nagasaki-city Nagasaki ,Japan

+81-95-819-7273

takahiro-takazono@nagasaki-u.ac.jp

Complete

Nov. 01, 2020

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1) Patients for whom voluntary written consent to participate in the study can be obtained personally
2) Patients aged 75 years or older at the time of informed consent
3) Presence of at least one each of the following general and respiratory symptoms associated with influenza, with severity of moderate or higher (with the exception of chronic symptoms or other symptoms that existed 30 days before the onset of influenza) at the time of informed consent and persisting at screening
a. General symptoms (headache, feverishness or chills, muscle or joint pain, or fatigue)
b. Respiratory symptoms (cough, sore throat, or nasal congestion)
4) Patients with fever of =>37.5 degrees Celsius (axillary) within 12 hours before pre-dose examination (screening )
5) Influenza-positive patients with rapid influenza diagnostic test at screening
**If a rapid influenza diagnostic test or any other influenza virus detection method has been already performed in routine clinical practice within 48 hours of onset as inclusion criteria 6), the results can be determined.
6) Patients in whom the time interval between the onset of symptoms and the pre-dose examination is 48 hours or less. Symptomatic onset is defined as follows:
a. Time of the first increase in body temperature (an increase by at least 1 degrees Celsius from normal body temperature)
b. Time when the patient newly experiences at least one general or respiratory symptom

1) Patients with severe influenza requiring hospitalization for treatment1) Patients with severe influenza requiring hospitalization for treatment
2) Patients who are allergic to baloxavir /oseltamivir or have a history of clinically relevant intolerance to baloxavir /oseltamivir
3) Patients who are severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or with suspected coronavirus disease 2019 (COVID-19)
4) Patients who are unable to swallow baloxavir tablets or oseltamivir capsules
5) Patients with any concurrent infection requiring systemic antimicrobial treatment at the time of screening
6) Patients with poorly controlled metabolic disease (including diabetes)
7) Patients on dialysis and patients with severe renal impairment (defined as eGFR of <30 mL/min/1,73m2)
8) Patients with congestive cardiac failure receiving pharmacological treatment
9) Patients with any major cardiovascular disease, central nervous system disease, endocrine disorder (thyroid function, adrenal function), hepatitis, or liver cirrhosis requiring hospitalization
10) Patients with malignancy receiving chemotherapy or immunotherapy
11) HIV-infected patients
12) Patients in an immunosuppressed state after organ or bone marrow transplant
13) Patients receiving continuous systemic prednisolone at >20 mg or equivalent doses of corticosteroids
14) Patients who received baloxavir marboxile (Xofluza), peramivir (Rapiacta), Laninamivir (Inavir), oseltamivir (Tamiflu, Oseltamivir Capsules 75mg "Sawai"), zanamivir (Relenza), or amantadine (Symmetrel) within 14 days before screening
15) Patients who will require prohibited concomitant medication during the study period in the opinion of the investigator/subinvestigator
16) Patients who are participating other clinical studies
17) Patients who had participated in this clinical study
18) Patients that the investigator/subinvestigator deems difficult to be participated to the study

Both

Influenza Virus Infection.

Among patients allocated to the baloxavir group, patients with <80 kg body weight at screening will receive two baloxavir 20-mg tablets, while patients with =>80 kg body weight at screening will receive four baloxavir 20-mg tablets.
Patients allocated to the oseltamivir group will receive one oseltamivir 75-mg capsule twice daily for 5 days.

Duration of influenza disease: Time to improvement of influenza symptoms (adjusted for existing symptoms)

1) Time to alleviation of the seven influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue)
2) Time to improvement of the four general symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue)
3) Time to improvement of the three respiratory symptoms (cough, nasal congestion, and sore throat)
4) Time to resolution of fever to normal temperature
5) Proportion of patients with resolution of fever to normal temperature at each time point of evaluation
6) Body temperature at each time point of evaluation
7) Influenza virus serum antibody titers at each time point of evaluation
8) Time to resolution of gastrointestinal symptoms (diarrhea and impaired appetite)
9) Time to improvement of each symptom of influenza
10) Proportion of patients who underwent additional treatments or procedures for underlying respiratory disease
11) Changes in respiratory function parameters (CAT total score, oxygen saturation [SpO2]) from baseline to each time point of evaluation, up to 2 weeks after the start of treatment
12) Time to return to pre-influenza health
13) Requirement for systemic antimicrobial use for influenza secondary infections
14) Incidence of influenza-related complications (hospitalization, death, sinusitis, bronchitis, otitis media, X-ray-documented pneumonia)
15) Household infection rate for influenza after the start of the study

+81-95-819-7229

Sept. 24, 2020

none