Influenza A VirusPhase 2ROSIINCT01010087
Trial Comparing High Versus Standard Dose Oseltamivir in Severe Influenza Infection in ICU
A Phase 2 study testing Oseltamivir in people with Influenza A Virus, run by University of Manitoba at 1 site in Canada.
Trial summary
Primary Objectives: The primary objective of the trial is to compare the antiviral efficacy of a 10 day course of standard (75 mg bid) and high-dose (225 mg bid) oseltamivir (or equivalent doses in mild-moderate renal failure) in the treatment of severe influenza infections. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Influenza A Virus
- What is being tested?
- Oseltamivir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2009to May 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients age 12 and older and 45 kg or more
- Suspected or confirmed influenza (Appendix A)
- Requirement for ICU admission due to respiratory distress or critical illness defined as one of:
- Inspired oxygen need of >50% for at least 4 hours (For FiO2 for non-intubated patients see Appendix B)
- mechanical ventilation
- Patient is receiving inotrope or vasopressor
- Negative b-HCG test or negative bedside urine test pending a confirmatory b-HCG test for pregnancy in women of childbearing age (12-60 years of age) will allow study entry
Who cannot join
- Inability to obtain consent
- Patients receiving more than two doses of 150 mg or higher oseltamivir in 36 hours before study entry
- Patients having received more than 3 doses of 75 mg oseltamivir immediately in 36 hours before study entry
- Age less than 12 years, or age <16 and weight less than 45 kg
- Unlikely to absorb enteral study drug (e.g. patients with partial or complete mechanical bowel obstruction, intestinal ischemia, infarction, and short bowel syndrome)
- Known allergy or hypersensitivity to oseltamivir
Show all 13Show fewer
- Pregnancy or breast feeding
- Previous enrollment in current study
- Concurrent involvement in an RCT examining an antiviral agent including other neuraminidase inhibitors, interferon-a and/or ribavirin
- Chronic renal failure requiring chronic hemodialysis
- Severe chronic liver disease (Child-Pugh Score 11-15)
- Anticipated death within 24 hours as judged by attending physician or local PI
- Patient carrying "do not intubate" order (a "no CPR" or "no defibrillate" or "no chest compressions" order alone is allowed)
Trial locations and contacts
1 site in 1 country.
Canada1 site
Winnipeg Regional Health Authority; Health Sciences Centre
Winnipeg, Manitoba, R3E 0Z3
About this study
Official title: A Randomized, Double-Blinded Controlled Trial Comparing High vs Standard Dose Oseltamivir in Severe, Influenza Infection in ICU. "ROSII Study"
Primary Objectives:
The primary objective of the trial is to compare the antiviral efficacy of a 10 day course of standard (75 mg bid) and high-dose (225 mg bid) oseltamivir (or equivalent doses in mild-moderate renal failure) in the treatment of severe influenza infections.
Read more
The hypothesis is that high dose oseltamivir will increase the proportion of patients with negative reverse transcriptase (RT)-PCR detection of influenza viral RNA (and viral culture, at selected sites) at Day 5 post-treatment.
An important secondary objective of the trial, which reflects the main clinical objective, is to determine the difference in the numbers of ventilator days between the standard-dose and high-dose groups
Read the detailed description
Primary Objectives:
The primary objective of the trial is to compare the antiviral efficacy of a 10 day course of standard (75 mg bid) and high-dose (225 mg bid) oseltamivir (or equivalent doses in mild-moderate renal failure) in the treatment of severe influenza infections.
The hypothesis is that high dose oseltamivir will increase the proportion of patients with negative reverse transcriptase (RT)-PCR detection of influenza viral RNA (and viral culture, at selected sites) at Day 5 post-treatment.
An important secondary objective of the trial, which reflects the main clinical objective, is to determine the difference in the numbers of ventilator days between the standard-dose and high-dose groups.
Secondary Objectives:
- Laboratory objectives:
- Assess viral RNA load and clearance from nasopharyngeal and tracheal aspirate (intubated) or oropharyngeal (non-intubated) samples by RT-PCR on days 1, 3, 5, 7, 10, 14 and 28 days
- Determine viral clearance by culture from nasopharyngeal and tracheal aspirate (intubated) or oropharyngeal (non-intubated) samples on days 1, 3, 5, 7, 10, 14 and 28 days at select hospital sites with culture capability
- Assess the pharmacokinetics of oseltamivir carboxylate and phosphate on Day 3 in suspected H1N1 patients with respiratory distress and/or critical illness requiring ICU care
- Characterize the inflammatory cytokine response on Day 1-3, 5, 7, 10, 14, 21 and 28 days to severe influenza stratified by standard-dose versus high-dose oseltamivir therapy.
- Assess leukocyte gene expression at day 1, 3, 5, 10 and 21 days using high throughput RNA assessment techniques
- Examine urine for biomarkers of disease and severe disease
- Clinical and Safety Objectives:
- Determine the difference in the number of ventilator days in the standard-dose and high-dose groups
- Determine tolerability of high-dose versus standard-dose oseltamivir as assessed by the number of serious, atypical and drug-related adverse events that are possibly or probably related to oseltamivir
- Assess other secondary efficacy variables including survival duration, hospital free days to day 60, ICU free days to day 60, and shock (ie vasopressor) and renal failure free (ie not requiring hemodialysis; ultrafiltration acceptable) days to day 28 in relation to high vs standard dose oseltamivir therapy
- Assess 60 day mechanical ventilation and ICU-free days stay in relation to high vs standard dose oseltamivir therapy
- Determine clinical criteria used by clinicians when electing to continue or re-initiate oseltamivir therapy beyond 10 study day treatment course
Tertiary Objectives: Exploratory Analyses
- Laboratory Objectives:
- Assess the relationship between pharmacokinetic variables on day 3 and measures of viral clearance
- Assess the frequency and genetic basis of antiviral resistance to oseltamivir during and after therapy
- Determine possible host genetic factors including HLA type that predispose to severe influenza
- Clinical and Safety Objectives:
- Determine differences in development and persistence of adverse clinical signs (fever, heart rate, hypotension), requirement for and duration of organ support (supplemental oxygen, vasopressor/inotropes, continuous renal replacement therapy) and occurrence and resolution of organ failure by Sequential Organ Failure Assessment (SOFA) score at days 7, 10, 14 and 28 as a consequence of high-dose versus standard-dose oseltamivir
- Determine impact of oseltamivir dosing on frequency of progression to mechanical ventilation among non-ventilated patients
- Conditions
- Influenza A Virus
- Being tested
- Oseltamivir
- Keywords
- patients admitted to ICU
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OseltamivirDrug
Also called Tamiflu
standard (75 mg bid) or high-dose (225 mg bid) oseltamivir
| Study group | Role | What they receive |
|---|---|---|
| Standard Oseltamivir dose 75 mg bid | Active comparator | Standard dosing Receives: Drug: Oseltamivir |
| High Dose Oseltamivir arm 225mg bid | Experimental | High dose arm of the study Receives: Drug: Oseltamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Negative reverse transcriptase (RT)-PCR detection of viral RNA in nasopharyngeal and tracheal aspirate (intubated) or oropharyngeal (non-intubated) samples at Day 5 among patients who require ICU admission due to respiratory distress.
Measured: Day 5 on study
Secondary outcomes (1)
Ventilator days up to 60 d (main clinical endpoint),
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionMay 2011
- Study completionMay 2011
Why it stopped: Patient population no longer available.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza A VirusStudies of the same condition, open and under way.
- More trials run by University of ManitobaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Investigators
- Anand Kumar, MD, Principal investigator, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01010087
- Sponsor's protocol ID
- 133312
- Acronym
- ROSII
- Status last verified
- Jun 2011
- First submitted
- 5 Nov 2009
- Last updated
- 10 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded Controlled Trial Comparing High vs Standard Dose Oseltamivir in Severe, Influenza Infection in ICU. "ROSII Study"
- ClinicalTrials.gov ID
- NCT01010087
- Acronym / sponsor ID
- ROSII / 133312
- Conditions
- Influenza A Virus
- Keywords
- patients admitted to ICU
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Patient population no longer available.
- Enrolment
- 59 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- Nov 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 9 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives:
The primary objective of the trial is to compare the antiviral efficacy of a 10 day course of standard (75 mg bid) and high-dose (225 mg bid) oseltamivir (or equivalent doses in mild-moderate renal failure) in the treatment of severe influenza infections.
The hypothesis is that high dose oseltamivir will increase the proportion of patients with negative reverse transcriptase (RT)-PCR detection of influenza viral RNA (and viral culture, at selected sites) at Day 5 post-treatment.
An important secondary objective of the trial, which reflects the main clinical objective, is to determine the difference in the numbers of ventilator days between the standard-dose and high-dose groups
Detailed description
Primary Objectives:
The primary objective of the trial is to compare the antiviral efficacy of a 10 day course of standard (75 mg bid) and high-dose (225 mg bid) oseltamivir (or equivalent doses in mild-moderate renal failure) in the treatment of severe influenza infections.
The hypothesis is that high dose oseltamivir will increase the proportion of patients with negative reverse transcriptase (RT)-PCR detection of influenza viral RNA (and viral culture, at selected sites) at Day 5 post-treatment.
An important secondary objective of the trial, which reflects the main clinical objective, is to determine the difference in the numbers of ventilator days between the standard-dose and high-dose groups.
Secondary Objectives:
- Laboratory objectives:
- Assess viral RNA load and clearance from nasopharyngeal and tracheal aspirate (intubated) or oropharyngeal (non-intubated) samples by RT-PCR on days 1, 3, 5, 7, 10, 14 and 28 days
- Determine viral clearance by culture from nasopharyngeal and tracheal aspirate (intubated) or oropharyngeal (non-intubated) samples on days 1, 3, 5, 7, 10, 14 and 28 days at select hospital sites with culture capability
- Assess the pharmacokinetics of oseltamivir carboxylate and phosphate on Day 3 in suspected H1N1 patients with respiratory distress and/or critical illness requiring ICU care
- Characterize the inflammatory cytokine response on Day 1-3, 5, 7, 10, 14, 21 and 28 days to severe influenza stratified by standard-dose versus high-dose oseltamivir therapy.
- Assess leukocyte gene expression at day 1, 3, 5, 10 and 21 days using high throughput RNA assessment techniques
- Examine urine for biomarkers of disease and severe disease
- Clinical and Safety Objectives:
- Determine the difference in the number of ventilator days in the standard-dose and high-dose groups
- Determine tolerability of high-dose versus standard-dose oseltamivir as assessed by the number of serious, atypical and drug-related adverse events that are possibly or probably related to oseltamivir
- Assess other secondary efficacy variables including survival duration, hospital free days to day 60, ICU free days to day 60, and shock (ie vasopressor) and renal failure free (ie not requiring hemodialysis; ultrafiltration acceptable) days to day 28 in relation to high vs standard dose oseltamivir therapy
- Assess 60 day mechanical ventilation and ICU-free days stay in relation to high vs standard dose oseltamivir therapy
- Determine clinical criteria used by clinicians when electing to continue or re-initiate oseltamivir therapy beyond 10 study day treatment course
Tertiary Objectives: Exploratory Analyses
- Laboratory Objectives:
- Assess the relationship between pharmacokinetic variables on day 3 and measures of viral clearance
- Assess the frequency and genetic basis of antiviral resistance to oseltamivir during and after therapy
- Determine possible host genetic factors including HLA type that predispose to severe influenza
- Clinical and Safety Objectives:
- Determine differences in development and persistence of adverse clinical signs (fever, heart rate, hypotension), requirement for and duration of organ support (supplemental oxygen, vasopressor/inotropes, continuous renal replacement therapy) and occurrence and resolution of organ failure by Sequential Organ Failure Assessment (SOFA) score at days 7, 10, 14 and 28 as a consequence of high-dose versus standard-dose oseltamivir
- Determine impact of oseltamivir dosing on frequency of progression to mechanical ventilation among non-ventilated patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Oseltamivir dose 75 mg bid | Active comparator | Drug: OseltamivirStandard dosing |
| High Dose Oseltamivir arm 225mg bid | Experimental | Drug: OseltamivirHigh dose arm of the study |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients age 12 and older and 45 kg or more
- Suspected or confirmed influenza (Appendix A)
- Requirement for ICU admission due to respiratory distress or critical illness defined as one of:
- Negative b-HCG test or negative bedside urine test pending a confirmatory b-HCG test for pregnancy in women of childbearing age (12-60 years of age) will allow study entry
Key exclusion criteria (13 listed)
- Inability to obtain consent
- Patients receiving more than two doses of 150 mg or higher oseltamivir in 36 hours before study entry
- Patients having received more than 3 doses of 75 mg oseltamivir immediately in 36 hours before study entry
- Age less than 12 years, or age <16 and weight less than 45 kg
- Unlikely to absorb enteral study drug (e.g. patients with partial or complete mechanical bowel obstruction, intestinal ischemia, infarction, and short bowel syndrome)
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: Tamiflustandard (75 mg bid) or high-dose (225 mg bid) oseltamivir | Drug | High Dose Oseltamivir arm 225mg bid, Standard Oseltamivir dose 75 mg bid |
Primary outcome
Negative reverse transcriptase (RT)-PCR detection of viral RNA in nasopharyngeal and tracheal aspirate (intubated) or oropharyngeal (non-intubated) samples at Day 5 among patients who require ICU admission due to respiratory distress.
Time frame: Day 5 on study
1 secondary outcome
Ventilator days up to 60 d (main clinical endpoint),
Time frame: 60 days
Results and safety
The study was stopped early (reason given: Patient population no longer available.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2011.
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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.
Anand Kumar, MD principal investigator
University of Manitoba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oseltamivir in people with Influenza A Virus, run by University of Manitoba at 1 site in Canada.
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 7 inclusion and 13 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: stopped early, as of the sponsor's last update on 10 Jun 2011. 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Patient population no longer available.). Results are not available in the source record.
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?
Negative reverse transcriptase (RT)-PCR detection of viral RNA in nasopharyngeal and tracheal aspirate (intubated) or oropharyngeal (non-intubated) samples at Day 5 among patients who require ICU admission due to respiratory distress. (time frame: Day 5 on study). 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 10 Jun 2011; AzTrials last refreshed its copy on 6 Nov 2026.