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城東病院総合内科 ブログ


イナビル吸入の効果 タミフルとの比較

ジャーナルクラブ 感染症

Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate versus Oseltamivir for Treatment of Influenza: A Double-Blind, Randomized, Noninferiority Clinical Trial

Clinical Infectious Diseases 2010; 51(10):1167–1175







A この試験の結果は信頼できるか
P p1168 METHODS Study design and patients.

Eligible patients were aged ≧20 years who presented within 36 h after the onset of influenza symptoms and who had an axillary temperature of ≧37.5℃ and a positive test result with use of a rapid influenza diagnostic kit.




The exclusion criteria were as follows: suspicion of infection with a bacterial species or noninfluenza virus within 1 week before enrollment; reported occurrence of any influenza-like symptom within 1 week before the onset of influenza; chronic respiratory disease; renal dysfunction; history of alcohol or drug abuse; or treatment with amantadine, zanamivir, or oseltamivir within 4 weeks. Pregnant women, breast-feeding women, and women who wished to become pregnant during the period of the trial were also excluded.



I & C  p1168 METHODS Randomization and masking.

assigned (1:1:1) to a 40-mg laninamivir octanoate, a 20-mg laninamivir octanoate, or an oseltamivir treatment group. Laninamivir octanoate was delivered by oral inhalation with use



O p1169 METHODS study outcome.

The primary end point was the time to illness alleviation, defined as the time from the initiation of trial treatment to the beginning of the first 21.5-h period in which all influenza symptoms were “absent” or “mild.”




p1168 METHODS Study design and patients.
multicenter, double-blind, randomized controlled trial



A③ 患者はそれぞれの治療群にどのように割り付けられたか?

p1168 METHODS Randomization and masking.

The computer-generated block random allocation




p1168 METHODS Randomization and masking.

The patients, investigators, and trial personnel were blinded to the allocation sequence throughout the trial with use of a double-dummy method. The administration of laninamivir octanoate and the first dose of oseltamivir.




P1170 METHODS Statistic analysis.

In the efficacy analysis, the full analysis set based on the intention-to-treat principle was defined as the primary analysis set, and the per protocol set was used in the sensitivity analysis. These analysis sets were used because the full analysis set and per protocol set are equally important in a noninferiority trial. The safety analysis included all the patients who had received at least 1 dose of trial treatment and had at least 1 safety assessment.

→Fig1も参照。非劣性試験であり、ITTとper protcol解析両方が行われている。副作用の評価は、一度でも薬を使用した患者が対象となっている



p1168 METHODS Randomization and masking.

Patients were allowed to use acetaminophen as a rescue medication for symptom relief, and its use was recorded. The concomitant use of other drugs was prohibited for 15 days.

→Table1で、ワクチンはlaminamivir40mgでワクチンが少し少ないかもしれないが、それ以外は同じだろう。表はないがper protcol解析でもグループ間の差はなかった。適宜アセトアミノフェンを使用できるとあるが、どちらの群でどの程度使用されているかの記載がない



p1169 METHODS Statistical analysis.

a sample size of 300 patients in each group was determined to achieve a power of at least 80% to show noninferiority at both dose levels of laninamivir octanoate with use of a Monte Carlo simulation.



B⑧a 結果はどのように示されたか? b 有意差はあるか?
p1170 RESULT, p1171 figure 2, p1172 table2

The time courses for illness alleviation were similar among the 3 groups (Figure 2). In the full analysis set, the median time to illness alleviation was 73.0, 85.8, and 73.6 h in the 40mg laninamivir octanoate, 20mg laninamivir octanoate, and oseltamivir groups, respectively (Table 2).

However, the time to illness alleviation was significantly shorter in the 40mg group than in the 20mg laninamivir octanoate group (95%CI, -18.2 to -0.4;p =.038).


c 副作用は


The most common adverse events were gastrointestinal events such as diarrhea, nausea, and vomiting. The event rates for diarrhea were 7.7%, 5.5%, and 7.7% in the 40-mg laninamivir octanoate, 20-mg laninamivir octanoate, and oseltamivir groups, respectively. For nausea, the rates were 1.2%, 2.1%, and 1.8%, respectively. For vomiting, the rates were 0.3%, 0.3%, and 2.4%, respectively. These events were mild to moderate and resolved within several days. Mild to moderate dizziness was observed only in patients receiving laninamivir octanoate (0.9% in the 40-mg laninamivir octanoate group and 1.8% of 326 patients in the 20-mg laninamivir octanoate group), but none of the patients discontinued the trial because of dizziness.