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

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: Peramivir

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China
      • Prince Of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Nelson Lee, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: January 22, 2016
• First Submitted That Met QC Criteria: January 26, 2016
• First Posted (Estimate): January 27, 2016

Study Record Updates

• Last Update Posted (Estimate): January 29, 2016
• Last Update Submitted That Met QC Criteria: January 28, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Peramivir
• Other Study ID Numbers: Peramivir in adult influenza_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO