Dataset Information

Efficacy of combination therapy with oseltamivir phosphate and azithromycin for influenza: a multicenter, open-label, randomized study.

ABSTRACT:

Background

Macrolides have antibiotic and immunomodulatory activities, which may have a favorable effect on the clinical outcome of patients with infections, including influenza. This study aimed to evaluate the effects of combination therapy with an anti-influenza agent, oseltamivir, and a single-dose formulation of azithromycin (AZM), which has been used for influenza-related secondary pneumonia, on influenza patients. The primary endpoint was a change in the expression levels of inflammatory cytokines. Secondary endpoints were the time required for resolution of influenza-related symptoms, incidence of complications, and adverse reactions.

Methods

Patients with seasonal influenza were enrolled in this multicenter, open-label, randomized study. Patients were stratified according to the presence of a high risk factor and were randomized to receive combination therapy with oseltamivir plus an extended-release formulation of AZM (combo-group) or oseltamivir monotherapy (mono-group).

Results

We enrolled 107 patients and randomized them into the mono-group (56 patients) or the combo-group (51 patients). All patients were diagnosed with influenza A infection, and none of the patients had comorbid pneumonia. Statistically significant differences were not observed in the expression levels of inflammatory cytokines and chemokines between the 2 groups. The maximum temperature in the combo-group was lower than that in the mono-group on day 3 through day 5 (p = 0.048), particularly on day 4 (p = 0.037).

Conclusion

To our knowledge, this is the first prospective, randomized, clinical trial of oseltamivir and AZM combination therapy for influenza. Although the difference in inflammatory cytokine expression level was not statistically significant, combination therapy showed an early resolution of some symptoms.

Name of registry

University hospital Medical Information Network (UMIN).

Trial registration no

UMIN000005371.

SUBMITTER: Kakeya H

PROVIDER: S-EPMC3954629 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy of combination therapy with oseltamivir phosphate and azithromycin for influenza: a multicenter, open-label, randomized study.

Kakeya Hiroshi H Seki Masafumi M Izumikawa Koichi K Kosai Kosuke K Morinaga Yoshitomo Y Kurihara Shintaro S Nakamura Shigeki S Imamura Yoshifumi Y Miyazaki Taiga T Tsukamoto Misuzu M Yanagihara Katsunori K Tashiro Takayoshi T Kohno Shigeru S

PloS one 20140314 3

<h4>Background</h4>Macrolides have antibiotic and immunomodulatory activities, which may have a favorable effect on the clinical outcome of patients with infections, including influenza. This study aimed to evaluate the effects of combination therapy with an anti-influenza agent, oseltamivir, and a single-dose formulation of azithromycin (AZM), which has been used for influenza-related secondary pneumonia, on influenza patients. The primary endpoint was a change in the expression levels of infla ...[more]

PMID: 24632748

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Project description:BackgroundThe pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19.MethodsIn this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (Ctrough) ≥20 mg/L at all measured time points after the second dose.ResultsSixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir Ctrough decreased significantly over time in both groups (p <0.01). Relative to day 2 (48 hrs), concentrations were 91.7% and 90.3% lower in the 1600/600 mg group and 79.3% and 89.5% lower in the 1800/800 mg group at day 7 and 10, respectively. In contrast, oseltamivir concentrations did not change significantly over time. A 2-compartment disposition model with first-order absorption and elimination described the observed favipiravir concentration-time data well. Modeling demonstrated that less than 50% of patients achieved Ctrough ≥20 mg/L for >80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza.ConclusionThe two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.

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Dataset Information

Efficacy of combination therapy with oseltamivir phosphate and azithromycin for influenza: a multicenter, open-label, randomized study.

Background

Methods

Results

Conclusion

Name of registry

Trial registration no

Publications

Efficacy of combination therapy with oseltamivir phosphate and azithromycin for influenza: a multicenter, open-label, randomized study.

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