Background: Peramivir is a neuraminidase inhibitor that offers a one-dose intravenously (IV) treatment option for influenza (versus 5 day oral dosing for oseltamivir, which is used more frequently). Prior studies conducted in outpatient and hospitalized patients have shown peramivir to be non-inferior to oseltamivir. We sought to compare outcomes of ED patients at high risk for influenza complications treated with peramavir versus oseltamivir.
Methods: A randomized controlled clinical trial was conducted over 2 influenza seasons 2015-2017 in 2 urban U.S. EDs. Patients were randomized to either oral (oseltamivir) or IV (peramivir) treatment. Patients who were ≥18 years, had a positive rapid molecular influenza test by xpert flu A/B assay, met CDC criteria for antiviral treatment with symptom onset < 96 hours, able to provide informed consent and comply with daily follow-up in person (inpatient) or phone assessments (outpatient) were eligible. Outcomes of antiviral treatment were measured by the validated FLU-PRO score, a 32-question clinical end-point indicator, for 14 days via patients’ daily diary. Patients were discharged or admitted based decision of the ED attending physician. Non-inferior t-test was performed to determine whether patients treated with peramivir were not appreciably worse than those treated with oseltamivir using FLU-PRO score.
Results: Overall, 847 influenza positive patients were encountered during the study period. Among them, 575 (68%) were approached, 284 met enrollment criteria, and 179 were enrolled. Among them, 75% were infected with influenza A virus and 25% with influenza B virus. 95 (53%) patients were randomized to IV treatment arm and 84 were to oral treatment arm. Average FLU-PRO score at baseline was similar between two groups (IV: 2.67 vs. oral: 2.52) and the score decreased over time for both groups (day 5: IV: 1.71 vs. oral: 1.62; day 10: IV: 1.48 vs. oral: 1.37; day 14: IV: 1.40 vs. oral: 1.33; all p<0.05 for significantly non-inferior). Influenza-related complications were similar between two groups (pneumonia: IV: 12% vs. oral: 14%) and there were no deaths after 28 days of enrollment in both groups.
Conclusions: This randomized study demonstrated that the outcomes of one-dose IV-administered peramivir was comparable to oseltamivir, indicating potential use of peramivir in influenza-infected patients in the ED.