High-Dose Versus Standard-Dose Oseltamivir to Treat Severe Influenza and Avian Influenza
Condition: Influenza; Avian Influenza; Severe Influenza
MeSH terms: Influenza, Human; Influenza in Birds
Intervention: Oseltamivir
Intervention description: Oseltamivir is a sialic acid analogue that potently and specifically inhibits the viral neuraminidases by competitively and reversibly interacting with the active enzyme site of influenza A and B viruses. Oseltamivir will be administered orally in standard formulations (capsules for adults and children at least 15 years of age; suspension for children younger than 15 years).
Intervention MeSH terms: Oseltamivir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 326.0
Sex: All
Minimum age: 1 Year
Healthy volunteers: No
Keywords: Antibody Response; Antiviral Efficacy; Bird Flu; Severe Respiratory Distress; Viral Replication and Shedding

Summary:

      Influenza, also known as the flu, is a contagious respiratory illness caused by influenza
      viruses. The illness can range in severity, from mild to severe to even death, and it causes
      an estimated 500,000 to 1,000,000 deaths worldwide each year. In the last several years,
      there have been increasing numbers of human cases of avian influenza, or bird flu. This trend
      may pose a threat of a future pandemic--worldwide outbreak of disease--with an avian
      influenza virus that can easily spread from person to person. Oseltamivir is an antiviral
      medication that is used to treat people with uncomplicated human influenza, and it may be
      effective in treating people with either severe human influenza or avian influenza. The
      purpose of this international study is to compare standard-dose oseltamivir versus high-dose
      oseltamivir for treating people who are hospitalized with severe human influenza or avian
      influenza.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least one of the following respiratory symptoms: cough, dyspnea, sore throat

          -  Evidence of severe influenza or avian influenza, as defined below

          -  Severe influenza infection criteria:

               1. Need for hospitalization

               2. One of the following:

                    1. New infiltrate on chest x-ray (or any infiltrate if no prior chest x-ray or
                       not known)

                    2. Severe tachypnea (more information on this criterion can be found in the
                       protocol)

                    3. Severe dyspnea

                    4. Arterial oxygen saturation of 92% or less on room air by trans-cutaneous
                       method

               3. Positive diagnostic testing for influenza, as defined by either rapid influenza
                  antigen (Ag) positive (A or B) or qualitative reverse transcriptase-polymerase
                  chain reaction (RT-PCR) positive for any influenza

               4. Illness (defined by onset of fever, respiratory symptoms, or constitutional
                  symptoms) began within 10 days before study enrollment

          -  Avian influenza infection criteria:

               1. Nasal wash, nasopharyngeal aspirate, endotracheal aspirate, nasal swab, or throat
                  swab that is RT-PCR positive influenza for H5 influenza

               2. Illness (defined by onset of fever, respiratory symptoms, or constitutional
                  symptoms) began within 14 days before study enrollment

        Exclusion Criteria:

          -  Received more than 72 hours of oseltamivir (six doses) within 14 days

          -  Received oseltamivir at higher than standard doses within the last 14 days or during
             current acute illness, whichever is longer

          -  History of allergy or severe intolerance of oseltamivir, as determined by the
             investigator

          -  Alternate explanation for the clinical findings, as determined by the investigator and
             with the information immediately available

          -  Creatine clearance less than 10 ml/minute

          -  Pregnant or breastfeeding