A randomized double-blind controlled study of laninamivir compared with oseltamivir for the treatment of influenza in patients with chronic respiratory diseases

doi:10.1007/s10156-012-0460-1

Journal of Infection and Chemotherapy

Volume 19, Issue 1, 2013, Pages 89-97

https://doi.org/10.1007/s10156-012-0460-1 Get rights and content

Abstract

Influenza infection tends to be severe in patients with chronic underlying diseases. This study evaluated the efficacy and safety of laninamivir octanoate, an inhaled neuraminidase inhibitor, for the treatment of influenza patients with chronic respiratory diseases; we conducted a double-blind, randomized controlled trial to compare the efficacy and safety of laninamivir octanoate and oseltamivir for the treatment of influenza in these patients. A total of 203 patients aged ≥20 years were randomized to receive either laninamivir octanoate or oseltamivir. The primary efficacy endpoint was the time to illness alleviation. This study is registered with JapicCTI; the registration number is JapicCTI-090940. The full analysis set (FAS) included a total of 201 patients (laninamivir group, n = 101; oseltamivir group, n = 100). Most patients had underlying bronchial asthma and 170 patients were infected with influenza A(H1N1)2009. The median time to illness alleviation was 64.7 h in the laninamivir group and 59.7 h in the oseltamivir group, with a difference of 5.0 h between the two groups (95 % confidence interval, −13.6 to 16.1 h). No adverse events specific to laninamivir octanoate were observed, and adverse events such as bronchospasm, which has been reported to be observed with other inhaled drugs related to laninamivir octanoate, did not occur. Laninamivir octanoate showed similar efficacy and safety to oseltamivir in the treatment of influenza, including that caused by influenza A(H1N1)2009, in patients with chronic respiratory diseases.

References (26)

N. Kawai et al.
Clinical effectiveness of oseltamivir for influenza A (H1N1) virus with H274Y neuraminidase mutation
J Infect
(2009)
K.G. Nicholson et al.
Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group
Lancet
(2000)
A.E. Fiore et al.
Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008
MMWR Recomm Rep
(2008)
The City of New York Department of Health and Mental Hygiene. In: New York City Department of Health and Mental Hygiene...
R. Zarychanski et al.
Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection
CMAJ
(2010)
A. Kumar
Early versus late oseltamivir treatment in severely ill patients with 2009 pandemic influenza A (H1N1): speed is life
J Antimicrob Chemother
(2011)
S. Jain et al.
Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009
N Engl J Med
(2009)
A.E. Fiore et al.
Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP)
MMWR Recomm Rep
(2011)
World Health Organization. Influenza A (H1N1) virus resistance to oseltamivir—2008/2009 influenza season, northern...
Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients—Seattle, Washington, 2009
MMWR Morb Mortal Wkly Rep
(2009)

S.B. Graitcer et al.

Characteristics of patients with oseltamivir-resistant pandemic (H1N1) 2009—United States

Emerg Infect Dis

(2011)

A. Watanabe et al.

Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: a double-blind, randomized, noninferiority clinical trial

Clin Infect Dis

(2010)

N. Sugaya et al.

Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection

Antimicrob Agents Chemother

(2010)

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Therefore, 153 studies were retrieved, of which, 95 were excluded after assessment. Finally, the remaining 58 studies with complete data were included for this network meta‐analysis [7,10–41]. The 58 studies included were published between 1997 and 2018.
The aim of this study was to use a network meta-analysis (NWA) to evaluate the relative efficacy and safety of various neuraminidase inhibitors (NAIs) in reducing the duration of influenza symptoms, and thereby, informing the selection of suitable therapeutic regimens for patients with influenza. We conducted a systematic review of randomized controlled trials comparing the clinical effects of four NAIs administered to patients with influenza and placebo. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry and through hand searching. We carried out NWA to compare the different regimens with each other and across subgroups of age and medical status (high-risk patients). A total of 58 two-arm studies were identified. Five regimens were efficacious in reducing the time to alleviation of influenza symptoms in all populations; this efficacy was comparable. No significant improvements were seen in combination therapy groups. The mean difference in the time to alleviation of symptoms ranged from 12.78 to 19.51 h. According to the summarized mean difference and surface under the cumulative ranking curve (SUCRA), peramivir (SUCRA = 82.6%), zanamivir (SUCRA = 64%), and oseltamivir (SUCRA = 55.1%) were the three top-ranking drugs for treating influenza. Zanamivir and peramivir were the preferred pharmacologic intervention among all investigated interventions based on the calculated “value preference of SUCRA.” This study is a network meta-analysis to explore the therapeutic effects of NAIs in patients with influenza. Peramivir might be the best choice for reducing the time to alleviation of symptoms.
Antivirals Against Influenza
2022, Comprehensive Pharmacology
Influenza viruses are an important cause of morbidity and mortality each year. Influenza A and B viruses are constantly evolving which results in seasonal epidemics. The natural reservoir for influenza A is aquatic birds, resulting in a large number of viral subtypes. Through genetic re-assortment with different subtypes, pandemic strains of influenza A can emerge. Zoonotic transmission of avian influenza can also occur, in some cases resulting in severe acute respiratory distress. This chapter will look at the current influenza antivirals that are available for the treatment of seasonal, pandemic and avian influenza. M2 proton channel blockers, neuraminidase inhibitors, and polymerase inhibitors will be discussed. The M2 proton blockers, amantadine and rimantadine, are only effective against influenza A viruses with influenza B viruses intrinsically resistant to these antivirals. Zanamivir, oseltamivir, peramivir and laninamivir are the neuraminidase inhibitors currently licensed for use to treat both influenza A and B viruses. The neuraminidase inhibitors prevent release of new viral progeny. The polymerase inhibitors, baloxavir and favipiravir, inhibit viral replication. However, amino acid substitutions can lead to reduced antiviral susceptibility and current surveillance of circulating influenza viruses is key to monitoring transmitted and treatment emergent influenza virus variants.
A Cost-Effectiveness Analysis of Neuraminidase Inhibitors for Influenza Virus Infections in an Adult-Outpatient Setting in Japan
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Citation Excerpt :
Because this report focused on the 5- to 19-year-old age group, abnormal behaviors are less likely to occur in adults. In addition, the efficacy of oseltamivir and laninamivir for patients with chronic respiratory diseases was examined in Japan, and this revealed that oseltamivir and laninamivir were similarly effective for patients with chronic respiratory diseases.23 However, when patients’ QOL was low according to our sensitivity analysis, laninamivir would be dominated.
Pharmacoeconomic studies have been less performed in Japan. The objective of this study was to clarify which neuraminidase inhibitor (NI; oseltamivir, zanamivir, laninamivir, and peramivir) is most cost-effective in an adult outpatient setting in Japan.
To clarify which neuraminidase inhibitor (NI; oseltamivir, zanamivir, laninamivir, and peramivir) is most cost-effective in an adult outpatient setting in Japan.
Cost-effectiveness analysis was constructed from the healthcare payer’s perspective. A decision tree model was constructed with probabilities from relevant randomized controlled trials. Costs included medical costs and drug prices. Medical costs were obtained from the medical fee schedule table (2016 version). We also applied authorized medication costs. Outcomes of effectiveness were measured using EQ-5D-3L questionnaires for adult patients who had experienced influenza virus infections previously. Time horizon was 14 days in this study.
Cost-effectiveness ratios for oseltamivir, zanamivir, laninamivir, and peramivir were 393 674 Yen/quality-adjusted life year (QALY; US$3883.41/QALY), 408 241 (US$4027.10), 407 980 (US$4024.53), and 444 264 (US$4382.45), respectively. The cost-effectiveness analysis base-case analysis revealed oseltamivir as the most cost-effective NI. Zanamivir was dominated. Incremental cost effectiveness ratio (ICER) for laninamivir and peramivir were 1 129 459 Yen/QALY (US$11 141.58/QALY) and 1 287 118 (US$12 696.81), respectively. One-way sensitivity analyses revealed that minimum ICERs for laninamivir based on “quality of life (QOL) values (95% confidence interval)” was −596 850 Yen/QALY (US−$5887.64/QALY) owing to high cost and less effective. Also, maximum ICER for peramivir based on“QOL values” was 14 717 518 Yen/QALY (US$145 181.32/QALY); a value more than the 5 000 000 Yen/QALY threshold.
The study results reveal oseltamivir as the most cost-effective NI for the treatment of influenza virus infection in an adult outpatient setting. Our findings may provide decision makers with scientific evidence for clinical and economic evaluation to achieve optimal therapeutic outcomes.
Respiratory Virus Infections of the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient
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Citation Excerpt :
There are several novel agents in development for treatment of influenza, although not much data is available in HCT recipients or HM patients. The NAI laninamivir octanoate is efficacious against oseltamivir-resistant strains and currently is used in Japan but is not yet Food and Drug Administration approved.76–78 S-033188, a selective inhibitor of influenza cap-dependent endonuclease, was recently Food and Drug Administration approved for uncomplicated influenza, including resistant strains, but has not yet been studied in complicated influenza or in this patient population.79
Clinical effectiveness of four neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) for children with influenza A and B in the 2014–2015 to 2016–2017 influenza seasons in Japan
2018, Journal of Infection and Chemotherapy
Citation Excerpt :
In Japan, almost all patients with an influenza-like illness are tested with rapid antigen tests, and they are treated with one of the NAIs when positive; this has become standard practice in clinics nationwide [7]. The clinical effectiveness of zanamivir, laninamivir, and peramivir has been tested mainly in clinical trials compared to the effect of either a placebo or oseltamivir [1,8–14], and there have been few studies in which the clinical effectiveness of four NAIs (oseltamivir, zanamivir, laninamivir, and peramivir) was compared [15,16]. In the present study, we evaluated the clinical effectiveness of the four NAIs for children with influenza A and B by comparing the durations of fever after administration of the first doses of NAIs.
The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014–2015 to 2016–2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1.06 per 1 year of age, p < 0.001) and that the duration of fever after administration of the first dose of the NAI was shorter in patients with influenza A infection than in patients with influenza B infection (hazard ratio = 2.21, p < 0.001). A logistic regression model showed that the number of biphasic fever episodes was 2.99-times greater for influenza B-infected patients than for influenza A-infected patients (p < 0.001). The number of biphasic fever episodes in influenza A- or B-infected patients aged 0–4 years was 2.89-times greater than that in patients aged 10–18 years (p = 0.010), and the number of episodes in influenza A- or B-infected patients aged 5–9 years was 2.13-times greater than that in patients aged 10–18 years (p = 0.012).
Antiviral Treatments
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A randomized double-blind controlled study of laninamivir compared with oseltamivir for the treatment of influenza in patients with chronic respiratory diseases

Abstract

J Infect

Lancet

Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008

MMWR Recomm Rep

Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection

CMAJ

Early versus late oseltamivir treatment in severely ill patients with 2009 pandemic influenza A (H1N1): speed is life

J Antimicrob Chemother

Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009

N Engl J Med

Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP)