Efficacy Study of Early Versus Late Oseltamivir Administration for Treating and Preventing Influenza

In the past decade influenza has become increasingly recognized as a serious disease and
pandemic threat. Elderly persons, young children, and individuals with chronic medical
conditions have the greatest risk for complications or death from influenza infection.
Neuraminidase inhibitors are currently licensed for the treatment and prevention of influenza
if started early in the course of illness, but little is known regarding the effects of
oseltamivir (one neuraminidase inhibitor) on illness severity when initiated later in the
course of illness. Greater knowledge of the treatment effects is urgently needed for optimal
management of seasonal influenza, and to maximize use of a limited stockpile of antiviral
drugs in the event of an influenza pandemic.

Inclusion criteria:

1. Outpatient or inpatient encounter for acute respiratory illness less than 5 days (120
hours) duration.

2. Acute respiratory illness with feverishness OR cough.

3. Access to the internet or telephone at home. This is required because symptom severity
reports will be submitted twice daily using either a secure web-based form or
automated telephone entry. All phones in the Marshfield area have touchtone service,
allowing automated data entry.

Exclusion criteria:

1. Institutional resident (including assisted living or skilled nursing facility).

2. Self-reported chronic liver or kidney disease. These conditions are listed as
precautions in the oseltamivir manufacturer package insert
(www.rocheusa.com/products/tamiflu/pi.pdf).

3. Pregnancy or breast-feeding. Oseltamivir is classified as pregnancy category C, and it
is excreted in breast milk. The package insert states that the drug should be used
only if the potential benefit justifies the potential risk to the fetus or breast-fed
infant.

4. Prior hypersensitivity reaction to oseltamivir.

5. Dementia, impaired communication, or other reason for inability to provide informed
consent.

6. Immunocompromised status, including HIV infection, neutropenia, systemic
corticosteroid use, or use of other immunosuppressive drugs in the past 30 days. The
manufacturer states that the efficacy of oseltamivir has not been established in
immunocompromised patients.

7. Patient received 1 or more doses of influenza antiviral agents (oseltamivir,
zanamivir, amantadine, rimantadine) or a prescription for one of these drugs prior to
randomization.