さまよう薬剤師のブログ

感染症治療を考える素材を提供します。最近は意思決定への応用が関心領域。双子と0歳の育児奮闘中。I have Ph.D. but less sense a ID pharmacist (ICPS). Another face is an investor.

インフルエンザ 治療 RCT (2016-2018) 振り返る

インフルエンザシーズンなので、

2016からの有名なインフルエンザRCT論文をピックアップ。

 

 

 

Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents.

The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001).The time to alleviation of symptoms was similar with baloxavir and oseltamivir.

 

感想 : 症状改善が、約1日も短縮した。症状改善が、約1日しか短縮しなかった。

1回投与はいいのですが、もっとインパクト強かったらよかったのですが。

アドヒアランスより、約10%の耐性がフォーカスされている現状。

友人医師たちに聞くと、

処方後に、インフルエンザ外来患者をフォローすることは少ないため、耐性の臨床的

インパクトはあまり感じないと。

リアルワールド報告を待ちたいところです。なお、院内採用はしていません。

 

Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial.

80 (40·0%) of 200 participants in the combination group had detectable virus at day 3 compared with 97 (50·0%) of 194 (mean difference 10·0, 95% CI 0·2-19·8, p=0·046) in the monotherapy group.

 

感想 : phase 2 ですが、辛うじて有意な差をつけた。ただし、このプライマリーアウトカムがどの程度の臨床インパクトがあるのだろうか?ただし、興味深い検討であり。phase 3の結果待ちたい。

 

Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized, Controlled, Phase IIb/III Trial.

The combination treatment was associated with lower 30-day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001).

 

感想 : 興味深い併用の検討。マクロライド大好き日本で差は着くのだろうか?

 

Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial.

Compared with a median time to clinical response of 5·14 days in the 600 mg intravenous zanamivir group, the median time to clinical response was 5·87 days (difference of -0·73 days, 95% CI -1·79 to 0·75; p=0·25) in the 300 mg intravenous zanamivir group and 5·63 days (difference of -0·48 days, 95% CI -2·11 to 0·97; p=0·39) in the oseltamivir group.

 

感想 : ザナミビル600mg と300mgやオセルタミビルは差がなさそう。

 

Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study.

Of the participants with confirmed influenza (by PCR), 28 (67%) of 42 in the plasma plus standard care group normalised their respiratory status by day 28 compared with 24 (53%) of 45 participants on standard care alone (p=0·069). The hazard ratio (HR) comparing plasma plus standard care with standard care alone was 1·71 (95% CI 0·96-3·06).  

 

感想 : 差がなさそう。 

 

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children.

The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, -0.17 to 0.21) per child.  

 

 感想 : 差がなさそう。お手軽だったのですが、残念。

 

 

最後に、UP To Date より

 

Target groups for therapy

Given the concerning trends of increasing resistance with both the adamantanes and the neuraminidase inhibitors, the risk of promoting antiviral drug resistance should be considered when deciding which patients to treat. Individuals with severe disease (requiring hospitalization or evidence of lower respiratory tract infection) or at high risk for complications should receive antiviral therapy.

 

When indicated, antiviral therapy should be initiated as soon as possible since antiviral therapy is most likely to provide benefit when initiated within the first 48 hours of illness. Treatment should not be delayed while awaiting the results of diagnostic testing, nor should it be withheld in patients with indications for therapy who present >48 hours after the onset of symptoms, particularly among patients requiring hospitalization. Furthermore, patients who have a negative rapid antigen test for influenza but in whom the clinical suspicion for influenza infection is high should be treated with antivirals since the sensitivity of these tests may be low. 

 

We recommend antiviral therapy (with oseltamivir) for all individuals with confirmed or suspected influenza virus infection who are severely ill, such as those with lower respiratory tract infection (eg, dyspnea, tachypnea, unexplained oxygen desaturation), and those who are showing signs of rapid clinical deterioration; we recommend treatment for such patients whether they present early in the course of infection (<48 hours after symptom onset) (Grade 1B) or later (Grade 1C). 

 

We recommend antiviral therapy (with oseltamivir or zanamivir) for outpatients who present within 48 hours of symptom onset with confirmed or suspected influenza infection and who are at increased risk for complications (Grade 1A). We also recommend antiviral therapy for outpatients who present >48 hours after symptom onset with confirmed or suspected influenza infection and who are at increased risk for complications provided that they are not yet improving (Grade 1C). 

 

We suggest antiviral therapy with oseltamivirzanamivir, or baloxavir for patients who present within 48 hours of symptom onset with mild illness and who are not at increased risk for complications (Grade 2C). There is high quality evidence for benefit to the individual patient; however, there is only low quality evidence regarding the magnitude of the risk of promoting resistance, which remains a major concern. Additionally, when supplies are limited, antivirals should be reserved for high-risk patients. 

 

We recommend that patients with uncomplicated influenza who have had more than 48 hours of influenza signs and symptoms not be treated with antivirals (Grade 1B).

 

Management of pregnant women is discussed separately. 

 

Choice of antiviral agent

Clinicians should review local or state influenza surveillance data during influenza season to determine which types of influenza (A or B) and subtypes of influenza A (H1N1 or H3N2) are circulating, as well as antiviral resistance patterns.

 

A neuraminidase inhibitor (oseltamivir or zanamivir) or the inhibitor of influenza cap-dependent endonuclease (baloxavir) can be used for the treatment of patients with uncomplicated influenza infection. Oseltamivir is currently the preferred drug for severe influenza. 

 

The dosing of antiviral agents for influenza is summarized in the following table (table 2). The recommended duration of therapy for zanamivir or oseltamivir is five days. Peramivir and baloxavir are given as a single dose.

 

Because of the high rates of influenza isolates resistant to adamantanes in the United States and in many other countries, amantadine and rimantadine are not recommended for the treatment of influenza.

 

 

 

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