title: Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients.
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.
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Menno D
authors.initials: MD
authors.lastname: de Jong
authors.affiliation: Division of Infectious Disease and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ison
authors.affiliation: School of Public Health, University of Michigan, Ann Arbor.
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Monto
authors.affiliation: Pneumology Department, SHATPPD-Ruse, Ruse, Bulgaria.
authors.forename: Hristo
authors.initials: H
authors.lastname: Metev
authors.affiliation: Emergency Medicine Observation Unit, William Beaumont Hospital, Royal Oak.
authors.forename: Carol
authors.initials: C
authors.lastname: Clark
authors.affiliation: Department of Emergency Medicine, Wayne State University-Detroit Medical Center, Michigan.
authors.forename: Brian
authors.initials: B
authors.lastname: O'Neil
authors.affiliation: PharPoint Research, Wilmington.
authors.forename: Jenna
authors.initials: J
authors.lastname: Elder
authors.affiliation: BioCryst Pharmaceuticals, Durham, North Carolina.
authors.forename: Amy
authors.initials: A
authors.lastname: McCullough
authors.affiliation: BioCryst Pharmaceuticals, Durham, North Carolina.
authors.forename: Phil
authors.initials: P
authors.lastname: Collis
authors.affiliation: BioCryst Pharmaceuticals, Durham, North Carolina.
authors.forename: William P
authors.initials: WP
authors.lastname: Sheridan
mesh_terms: D000146:Acids, Carbocyclic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D003517:Cyclopentanes / Q000627:therapeutic use*; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D006760:Hospitalization; D006801:Humans; D007251:Influenza, Human / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; C414210:peramivir
keywords: clinical trial; hospitalized; influenza; peramivir