Clinical trial NCT00555893: Efficacy Study of Early Versus Late Oseltamivir Administration for Treating and Preventing Influenza
Official title: Monitoring Influenza Severity on Tamiflu (MIST)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Influenza
Keywords: randomized
blinded
controlled
efficacy
Lead sponsor: Marshfield Clinic Research Foundation
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2007-11-09
Enrollment: 194
Sex: ALL
Minimum age (years): 1
Maximum age (years): 79
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, blinded, placebo-controlled clinical efficacy trial to assess the duration and severity of influenza symptoms, and duration of viral shedding, in influenza patients receiving oseltamivir early and late relative to placebo.

There are two main hypotheses in this study:

1. The duration of influenza symptoms, mean severity score, and duration of viral shedding are reduced in patients who initiate oseltamivir treatment late (48 to 119 hours) compared to those receiving no antiviral therapy.
2. Prior influenza vaccination (same season) reduces the duration of influenza symptoms and mean symptom severity in patients receiving oseltamivir after adjusting for age and timing of antiviral therapy (early versus late).

There are two secondary hypotheses:

1. The duration of influenza symptoms, mean severity score, and duration of viral shedding are reduced in patients with influenza who initiate oseltamivir treatment early (\< 48 hours) versus late (48 to 119 hours).
2. The incidence of secondary complications is lower in patients initiating oseltamivir therapy late relative to those receiving no antiviral therapy.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Duration of Influenza Illness
timeFrame: Interval (in 12 hour blocks) from time of randomization until resolution (minimum 7 days, maximum 14 days)
Secondary outcomes:
measure: Mean Illness Severity Score
timeFrame: Calculated from initial enrollment (randomization) up to first period of symptom resolution (minimum of 7 days, maximum of 14 days)
measure: Viral Shedding on Day 3-4 of Treatment
timeFrame: 3-4 days after treatment initiation
measure: Secondary Complications (Otitis Media, Sinusitis, Pneumonia, Hospital Admission)
timeFrame: 30 days from symptom onset
measure: Mean Influenza Well-being Score
timeFrame: Randomization to resolution
Other outcomes:
Locations:
city: Marshfield
country: United States
facility: Marshfield Clinic Research Foundation
state: Wisconsin
Study officials:
affiliation: Marshfield Clinic Research Foundation
name: Edward Belongia, MD
role: PRINCIPAL_INVESTIGATOR
References: