InfluenzaNCT00555893
Efficacy Study of Early Versus Late Oseltamivir Administration for Treating and Preventing Influenza
A study testing Oseltamivir in people with Influenza, run by Marshfield Clinic Research Foundation at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 79 years
- Conditions the study is for
- Influenza
- What is being tested?
- Oseltamivir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 194 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Feb 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 79 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Marshfield Clinic Research Foundation
Marshfield, Wisconsin, 54449
About this study
Official title: Monitoring Influenza Severity on Tamiflu (MIST)
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:
Read more
- 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.
Read the 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
- Being tested
- Oseltamivir, Placebo
- Keywords
- randomized, blinded, controlled, efficacy
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OseltamivirDrug
Also called Tamiflu
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)
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Interval (in 12 hour blocks) from time of randomization until resolution (minimum 7 days, maximum 14 days)
Secondary outcomes (4)
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.
Measured: 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
Proportion of participants with positive PCR on day 3-4 of treatment
Measured: 3-4 days after treatment initiation
Secondary Complications (Otitis Media, Sinusitis, Pneumonia, Hospital Admission)
Measured: 30 days from symptom onset
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.
Measured: Randomization to resolution
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2007 (estimated)
- Study startJan 2008
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marshfield Clinic Research Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Principal investigator, Edward Belongia, Marshfield Clinic Research Foundation
- Investigators
- Edward Belongia, MD, Principal investigator, Marshfield Clinic Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00555893
- Sponsor's protocol ID
- 1U01IP000124-01
- Status last verified
- Oct 2018
- First submitted
- 7 Nov 2007
- Last updated
- 16 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monitoring Influenza Severity on Tamiflu (MIST)
- ClinicalTrials.gov ID
- NCT00555893
- Acronym / sponsor ID
- 1U01IP000124-01
- Conditions
- Influenza
- Keywords
- randomized, blinded, controlled, efficacy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 194 participants (actual)
- Lead sponsor
- Marshfield Clinic Research FoundationUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- Jan 2008
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 9 Nov 2007 (estimated)
- Results
- Posted 14 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Drug | Experimental | Drug: OseltamivirAdults 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 | Placebo comparator | Drug: PlaceboIdentical 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. |
Who may qualify
- Ages
- 1 year to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OseltamivirAlso: TamifluAdults 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 | Active Drug |
| PlaceboIdentical 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 |
Primary outcome
Duration of Influenza Illness
Time frame: Interval (in 12 hour blocks) from time of randomization until resolution (minimum 7 days, maximum 14 days)
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.
4 secondary outcomes
Mean Illness Severity Score
Time frame: 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
Time frame: 3-4 days after treatment initiation
Secondary Complications (Otitis Media, Sinusitis, Pneumonia, Hospital Admission)
Time frame: 30 days from symptom onset
Mean Influenza Well-being Score
Time frame: Randomization to resolution
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward Belongia, MD principal investigator
Marshfield Clinic Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oseltamivir in people with Influenza, run by Marshfield Clinic Research Foundation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of Influenza Illness (time frame: Interval (in 12 hour blocks) from time of randomization until resolution (minimum 7 days, maximum 14 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2018.