Back to resultsEfficacy Study of Early Versus Late Oseltamivir Administration for Treating and Preventing Influenza
Primary Purpose
Influenza
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Oseltamivir
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Influenza focused on measuring randomized, blinded, controlled, efficacy
Eligibility Criteria
Inclusion criteria:
- 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.
Exclusion criteria:
- 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.
Sites / Locations
- Marshfield Clinic Research Foundation
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Active Drug
Placebo
Arm Description
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)
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Mean Illness Severity Score
Mean severity score will be calculated by first summing the symptom severity scores for all reporting periods from initial enrollment (randomization) up to (and including) the first period of symptom resolution, as defined above. The summed total will be divided by the number of reporting periods to yield the mean severity score for each participant. For each reporting period, the possible symptom scores will range from 0 (all symptoms absent) to 24 (all symptoms severe). For children less than 2 years old, the possible scores will range from 0 to 15.
Viral Shedding on Day 3-4 of Treatment
Proportion of participants with positive PCR on day 3-4 of treatment
Secondary Complications (Otitis Media, Sinusitis, Pneumonia, Hospital Admission)
Mean Influenza Well-being Score
Mean influenza wellbeing score is calculated by first summing the daily scores for overall health (0-9 points), ability to perform usual activities (0-9 points), and sleep quality (0-9 points) from initial enrollment (randomization) up to (and including) the first day of symptom resolution. This is divided by the number of reporting days to yield the mean daily influenza wellbeing score for each person. Minimum score is 0 and maximum is 27. Higher scores indicate better outcome.
Full Information
NCT ID
NCT00555893
First Posted
November 7, 2007
Last Updated
October 15, 2018
Sponsor
Marshfield Clinic Research Foundation
Collaborators
Centers for Disease Control and Prevention
1. Study Identification
Unique Protocol Identification Number
NCT00555893
Brief Title
Efficacy Study of Early Versus Late Oseltamivir Administration for Treating and Preventing Influenza
Official Title
Monitoring Influenza Severity on Tamiflu (MIST)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Marshfield Clinic Research Foundation
Collaborators
Centers for Disease Control and Prevention
4. Oversight
Data Monitoring Committee
No
5. Study Description
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:
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.
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:
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
randomized, blinded, controlled, efficacy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
194 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active Drug
Arm Type
Experimental
Arm Description
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)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Name(s)
Oseltamivir
Other Intervention Name(s)
Tamiflu
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Duration of Influenza Illness
Description
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.
Time Frame
Interval (in 12 hour blocks) from time of randomization until resolution (minimum 7 days, maximum 14 days)
Secondary Outcome Measure Information:
Title
Mean Illness Severity Score
Description
Mean severity score will be calculated by first summing the symptom severity scores for all reporting periods from initial enrollment (randomization) up to (and including) the first period of symptom resolution, as defined above. The summed total will be divided by the number of reporting periods to yield the mean severity score for each participant. For each reporting period, the possible symptom scores will range from 0 (all symptoms absent) to 24 (all symptoms severe). For children less than 2 years old, the possible scores will range from 0 to 15.
Time Frame
Calculated from initial enrollment (randomization) up to first period of symptom resolution (minimum of 7 days, maximum of 14 days)
Title
Viral Shedding on Day 3-4 of Treatment
Description
Proportion of participants with positive PCR on day 3-4 of treatment
Time Frame
3-4 days after treatment initiation
Title
Secondary Complications (Otitis Media, Sinusitis, Pneumonia, Hospital Admission)
Time Frame
30 days from symptom onset
Title
Mean Influenza Well-being Score
Description
Mean influenza wellbeing score is calculated by first summing the daily scores for overall health (0-9 points), ability to perform usual activities (0-9 points), and sleep quality (0-9 points) from initial enrollment (randomization) up to (and including) the first day of symptom resolution. This is divided by the number of reporting days to yield the mean daily influenza wellbeing score for each person. Minimum score is 0 and maximum is 27. Higher scores indicate better outcome.
Time Frame
Randomization to resolution
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
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.
Exclusion criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Belongia, MD
Organizational Affiliation
Marshfield Clinic Research Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Marshfield Clinic Research Foundation
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
12. IPD Sharing Statement
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Efficacy Study of Early Versus Late Oseltamivir Administration for Treating and Preventing Influenza
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