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

NCT ID: NCT00555893

Last Updated: 2018-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2011-02-28

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.

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active Drug

Adults and adolescents weighing greater than 88 pounds will receive one 75 mg oseltamivir capsule twice daily, with or without food for a total of 5 days (10 doses). Participants one year of age and older up to a maximum weight of 88 pounds will receive a liquid form of study medication containing oseltamivir at a concentration of 15mg/ml. The dose will be based on weight:

for weight <=33 lbs, dose=30 mg, volume per dose (15mg/mL)=2 mL two times per day x 5 days (10 doses); for weight 34-51 lbs, dose=45 mg, volume per dose (15mg/mL)=3 mL two times per day x 5 days (10 doses); for weight 52-88 lbs, dose=60 mg, volume per dose (15mg/mL)= 4 mL two times per day x 5 days (10 doses)

Group Type: EXPERIMENTAL

Oseltamivir

Intervention Type: DRUG

Adults and adolescents weighing greater than 88 pounds will receive one 75 mg oseltamivir capsule twice daily, with or without food for a total of 5 days (10 doses). Participants one year of age and older up to a maximum weight of 88 pounds will receive a liquid form of study medication containing oseltamivir at a concentration of 15mg/ml. The dose will be based on weight:

for weight <=33 lbs, dose=30 mg, volume per dose (15mg/mL)=2 mL two times per day x 5 days (10 doses); for weight 34-51 lbs, dose=45 mg, volume per dose (15mg/mL)=3 mL two times per day x 5 days (10 doses); for weight 52-88 lbs, dose=60 mg, volume per dose (15mg/mL)= 4 mL two times per day x 5 days (10 doses)

Placebo

Identical placebo capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a placebo syrup. The dose will be based on weight as follows: \<=33 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Identical placebo capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a placebo syrup. The dose will be based on weight as follows: \<=33 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day.

Interventions

Oseltamivir

Adults and adolescents weighing greater than 88 pounds will receive one 75 mg oseltamivir capsule twice daily, with or without food for a total of 5 days (10 doses). Participants one year of age and older up to a maximum weight of 88 pounds will receive a liquid form of study medication containing oseltamivir at a concentration of 15mg/ml. The dose will be based on weight:

for weight <=33 lbs, dose=30 mg, volume per dose (15mg/mL)=2 mL two times per day x 5 days (10 doses); for weight 34-51 lbs, dose=45 mg, volume per dose (15mg/mL)=3 mL two times per day x 5 days (10 doses); for weight 52-88 lbs, dose=60 mg, volume per dose (15mg/mL)= 4 mL two times per day x 5 days (10 doses)

Intervention Type: DRUG

Placebo

Identical placebo capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a placebo syrup. The dose will be based on weight as follows: \<=33 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day.

Intervention Type: DRUG

Other Intervention Names

Tamiflu

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Marshfield Clinic Research Foundation

OTHER

Sponsor Role: lead

Responsible Party

Edward Belongia

Senior Research Scientist, Director Epidemiology Research Center, Marshfield Clinic Research Foundation

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Edward Belongia, MD

Role: PRINCIPAL_INVESTIGATOR

Marshfield Clinic Research Foundation

Locations

Marshfield Clinic Research Foundation

Marshfield, Wisconsin, United States

Countries

United States

Other Identifiers

1U01IP000124-01

Identifier Type: NIH

Identifier Source: org_study_id

View Link