Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients

Menno D. De Jong*, Michael G. Ison, Arnold S. Monto, Hristo Metev, Carol Clark, Brian O'Neil, Jenna Elder, Amy McCullough, Phil Collis, William P. Sheridan

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background. Seasonal influenza causes >200 000 annual hospitalizations in the United States. Current antiviral treatment options are limited to oral or inhaled agents. There is an urgent unmet need for intravenous antiviral treatments. Methods. Patients hospitalized with suspected influenza were randomized to 5-day treatment with intravenous peramivir (600 mg once daily) or placebo; all received the institution's standard of care (SOC) treatment. Time to clinical resolution and change in viral shedding in nasopharyngeal specimens were the primary and key secondary end points. Results. Influenza infection was confirmed in 338 of 405 enrolled patients. At the time of a preplanned interim analysis, the primary efficacy analysis population comprised 121 patients who did not receive a concurrent neuraminidase inhibitor as part of the SOC. The median (95% confidence interval) time to clinical resolution was 42.5 (34.0-57.9) hours for peramivir versus 49.5 (40.0-61.9) hours for placebo (P =.97). A larger treatment effect was observed in patients with history of symptoms <48 hours or admitted to an intensive care unit. Greater reductions in viral shedding, based on median tissue culture infective dose, were observed in patients who received peramivir than in placebo recipients, although this difference was not statistically significant. The incidence and severity of adverse events and laboratory abnormalities were similar between the 2 treatment groups. The study was terminated for futility after a preplanned interim analysis. Conclusions. A significant clinical benefit was not demonstrated for peramivir plus SOC compared with placebo plus SOC. Peramivir was generally safe and well tolerated. These findings highlight the challenges in designing studies to evaluate influenza antiviral agents in a hospitalized setting. Clinical Trials Registration. NCT00958776.

Original languageEnglish (US)
Pages (from-to)e172-e185
JournalClinical Infectious Diseases
Volume59
Issue number12
DOIs
StatePublished - Dec 15 2014

Fingerprint

Human Influenza
Standard of Care
Placebos
Antiviral Agents
Virus Shedding
Therapeutics
Medical Futility
Neuraminidase
Intensive Care Units
peramivir
Hospitalization
Clinical Trials
Confidence Intervals
Incidence
Infection
Population

Keywords

  • clinical trial
  • hospitalized
  • influenza
  • peramivir

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

De Jong, M. D., Ison, M. G., Monto, A. S., Metev, H., Clark, C., O'Neil, B., ... Sheridan, W. P. (2014). Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients. Clinical Infectious Diseases, 59(12), e172-e185. https://doi.org/10.1093/cid/ciu632
De Jong, Menno D. ; Ison, Michael G. ; Monto, Arnold S. ; Metev, Hristo ; Clark, Carol ; O'Neil, Brian ; Elder, Jenna ; McCullough, Amy ; Collis, Phil ; Sheridan, William P. / Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients. In: Clinical Infectious Diseases. 2014 ; Vol. 59, No. 12. pp. e172-e185.
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De Jong, MD, Ison, MG, Monto, AS, Metev, H, Clark, C, O'Neil, B, Elder, J, McCullough, A, Collis, P & Sheridan, WP 2014, 'Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients', Clinical Infectious Diseases, vol. 59, no. 12, pp. e172-e185. https://doi.org/10.1093/cid/ciu632

Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients. / De Jong, Menno D.; Ison, Michael G.; Monto, Arnold S.; Metev, Hristo; Clark, Carol; O'Neil, Brian; Elder, Jenna; McCullough, Amy; Collis, Phil; Sheridan, William P.

In: Clinical Infectious Diseases, Vol. 59, No. 12, 15.12.2014, p. e172-e185.

Research output: Contribution to journalArticle

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T1 - Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients

AU - De Jong, Menno D.

AU - Ison, Michael G.

AU - Monto, Arnold S.

AU - Metev, Hristo

AU - Clark, Carol

AU - O'Neil, Brian

AU - Elder, Jenna

AU - McCullough, Amy

AU - Collis, Phil

AU - Sheridan, William P.

PY - 2014/12/15

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N2 - Background. Seasonal influenza causes >200 000 annual hospitalizations in the United States. Current antiviral treatment options are limited to oral or inhaled agents. There is an urgent unmet need for intravenous antiviral treatments. Methods. Patients hospitalized with suspected influenza were randomized to 5-day treatment with intravenous peramivir (600 mg once daily) or placebo; all received the institution's standard of care (SOC) treatment. Time to clinical resolution and change in viral shedding in nasopharyngeal specimens were the primary and key secondary end points. Results. Influenza infection was confirmed in 338 of 405 enrolled patients. At the time of a preplanned interim analysis, the primary efficacy analysis population comprised 121 patients who did not receive a concurrent neuraminidase inhibitor as part of the SOC. The median (95% confidence interval) time to clinical resolution was 42.5 (34.0-57.9) hours for peramivir versus 49.5 (40.0-61.9) hours for placebo (P =.97). A larger treatment effect was observed in patients with history of symptoms <48 hours or admitted to an intensive care unit. Greater reductions in viral shedding, based on median tissue culture infective dose, were observed in patients who received peramivir than in placebo recipients, although this difference was not statistically significant. The incidence and severity of adverse events and laboratory abnormalities were similar between the 2 treatment groups. The study was terminated for futility after a preplanned interim analysis. Conclusions. A significant clinical benefit was not demonstrated for peramivir plus SOC compared with placebo plus SOC. Peramivir was generally safe and well tolerated. These findings highlight the challenges in designing studies to evaluate influenza antiviral agents in a hospitalized setting. Clinical Trials Registration. NCT00958776.

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