Peramivir Treatment Response in Adults Hospitalized for Influenza-associated Lower Respiratory Tract Infections

Study Overview
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Brief Summary
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Peramivir is the first intravenous neuraminidase inhibitor (NAI) available for treatment of uncomplicated influenza in adults. Data from placebo-controlled trials in outpatients have shown antiviral efficacy, safety, and tolerability. Although the unmet need for intravenous therapy lies mainly with patients hospitalized with complicated diseases, such data are limited because of feasibility and ethical considerations for placebo-controlled studies. In this study, the investigators aimed to examine more specifically treatment effects of peramivir in adults hospitalized with influenza-associated lower respiratory tract complications (LRTC). Such findings may have important implications on clinical management.

Detailed Description
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The primary objective was to assess the virologic response of peramivir in influenza-associated lower respiratory tract complications (LRTC). The secondary objective was to assess safety and tolerability. Adults confirmed with influenza by polymerase chain reaction (PCR) and/or immunofluorescence assays during the seasonal peaks of 2011-2014 were assessed for eligibility. Consented individuals were randomized to receive either peramivir 600mg every 24 hourly or 300mg every 12 hourly for 5 days. In subjects not achieving clinical resolution by day 5, the same regimen could be continued until day 10 (virologic results unknown to clinicians).Renal-dosage adjustment, if required, was performed according to protocol. The study's primary endpoint was change in influenza RNA load over time. The secondary endpoints were viral shedding indicated by culture and RNA negativity at day 5, and drug tolerability. Additionally, a priori comparisons of these endpoints with historical controls treated with standard courses of oral oseltamivir (75mg bid for 5 days) in the same clinical settings were performed.

Official Title
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A Phase 2, Pilot, Open-label, Randomized Study of the Antiviral Activity, Safety, and Tolerability of Intravenous Peramivir in Adult Hospitalized Subjects With Confirmed Influenza Infection

Conditions
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Influenza

Intervention / Treatment
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* Drug: Peramivir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: symptoms/signs of influenza, and confirmation of lower respiratory tract infection (e.g. radiographic pneumonia, dyspnea caused by acute exacerbation of underlying airway diseases, bronchitis, or combinations). Exclusion Criteria: late presentation >1 week from onset, hemodynamic instability, hepatic/renal failure, dialysis, immunosuppression (e.g. transplant, chemotherapy), and pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Peramivir 300mg Q12H<br>Peramivir 300 mg, administered intravenously, twice daily (every 12 hours) | Drug: Peramivir<br>* The two regimens of Peramivir were compared<br>* Other names: intravenous neuraminidase inhibitor;|
| Active Comparator: Peramivir 600mg Q24H<br>Peramivir 600 mg, administered intravenously, once daily (every 24 hrs) | Drug: Peramivir<br>* The two regimens of Peramivir were compared<br>* Other names: intravenous neuraminidase inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in influenza RNA load | 5-10 days | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| viral shedding indicated by PCR and culture negativity |  | 5 days |