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

NCT00555893 | Completed Results

• 1 other identifier: 1U01IP000124-01
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

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. 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. 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).
3. 3.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).
4. 4.The incidence of secondary complications is lower in patients initiating oseltamivir therapy late relative to those receiving no antiviral therapy.

Conditions

Influenza

Keywords

randomized; blinded; controlled; efficacy

Outcome Measures

Primary Outcomes (1)

• Duration of Influenza Illness

  Resolution is defined as occurring at the start of the first 24-hour period in which the total symptom score was less than or equal to 2 with no symptom rated higher than mild. Time to resolution was calculated from the time of randomization to symptom resolution in 12 hour increments.

  Interval (in 12 hour blocks) from time of randomization until resolution (minimum 7 days, maximum 14 days)

Secondary Outcomes (4)

• Mean Illness Severity Score

  Calculated from initial enrollment (randomization) up to first period of symptom resolution (minimum of 7 days, maximum of 14 days)

• Viral Shedding on Day 3-4 of Treatment

  3-4 days after treatment initiation

• Secondary Complications (Otitis Media, Sinusitis, Pneumonia, Hospital Admission)

  30 days from symptom onset

• Mean Influenza Well-being Score

  Randomization to resolution

Study Arms (2)

Active Drug

EXPERIMENTAL

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)

Drug: Oseltamivir

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Oseltamivir 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)

Also known as: Tamiflu

Active Drug

Placebo 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.

Placebo

Eligibility Criteria

• Age: 1 Year - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatient or inpatient encounter for acute respiratory illness less than 5 days (120 hours) duration.
• Acute respiratory illness with feverishness OR cough.
• 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.

You may not qualify if:

• Institutional resident (including assisted living or skilled nursing facility).
• 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).
• 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.
• Prior hypersensitivity reaction to oseltamivir.
• Dementia, impaired communication, or other reason for inability to provide informed consent.
• 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.
• 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.

Sponsors & Collaborators

• Marshfield Clinic Research Foundation: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Marshfield Clinic Research Foundation

Marshfield, Wisconsin, 54449, United States

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Oseltamivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Edward Belongia, MD
• Organization: Marshfield Clinic Research Foundation

belongia.edward@mcrf.mfldclin.edu

715-389-3783

Study Officials

• Edward Belongia, MD

  Marshfield Clinic Research Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Research Scientist, Director Epidemiology Research Center, Marshfield Clinic Research Foundation

Study Record Dates

• First Submitted: November 7, 2007
• First Posted: November 9, 2007
• Study Start: January 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: October 16, 2018
• Results First Posted: January 14, 2015

Record last verified: 2018-10

Locations

US (1)