Severe InfluenzaOPTIFLUNCT05375864
Early Oseltamivir Carboxylate Low Plasma Concentration in Patients Admitted to Intensive Care for Severe Influenza
A study testing Absorption test in people with Severe Influenza, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Introduction Pandemic and seasonal influenza epidemics can be associated with a high degree of morbidity and mortality, especially in patients developing severe influenza pneumonitis with the acute respiratory distress syndrome (ARDS) or the less frequent fulminant myocarditis. Early administration (i.e. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Influenza
- What is being tested?
- Absorption test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 1 siteFrance
- Study dates
- 1 Dec 2022to 1 Mar 2025
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients
- Confirmed severe influenza infection requiring intensive care with tracheal intubation for invasive mechanical ventilation (influenza ARDS with or without bacterial co-infection, cardiorespiratory decompensation of influenza origin, influenza myocarditis)
- Oseltamivir treatment administered through a gastric tube initiated since less than 24 hours (i.e. maximum two doses administered)
- Affiliation to a social security system or beneficiary (excluding AME)
- Written consent obtained (or under emergency procedures)
Who cannot join
- Pregnancy or breastfeeding women
- Weight less than 40 kg
- Zanamivir or other antiviral effective treatment received for more than 24 hours
- Other respiratory virus infection (including SARS-CoV-2)
- Contra-indication to esophageal tube insertion or use
- Child-Pugh C cirrhosis or severe liver insufficiency
Show all 11Show fewer
- Paracetamol allergy
- Ongoing participation in an interventional therapeutic trial (medicine that may interact with paracetamol or oseltamivir)
- Patient benefiting from AME (State Medical Aid)
- Patient deprived of liberty or under legal protection (guardianship or curatorship)
- For patients not included in an emergency situation: Inability, according to the investigator, to understand or refusal to sign the informed consent to participate in the study (non-French-speaking patient).
Trial locations and contacts
1 site in 1 country.
France1 site
Anne-Fleur Haudebourg
Créteil, 94010
Anne-Fleur Haudebourg, M.D, 01 45 17 85 06 ext. +33, annefleur.maignant@aphp.fr
Nicolas De PROST, M.D., Ph.D, 0145178637 ext. +33, nicolas.de-prost@aphp.fr
About this study
Official title: Prognostic Impact of Early Oseltamivir Carboxylate Low Plasma Concentration in Critically Ill Patients With Severe Influenza: a Prospective Cohort Study
Introduction
Pandemic and seasonal influenza epidemics can be associated with a high degree of morbidity and mortality, especially in patients developing severe influenza pneumonitis with the acute respiratory distress syndrome (ARDS) or the less frequent fulminant myocarditis. Early administration (i.e. in the first 48 hours) of the neuraminidase inhibitor oseltamivir is associated with reduced mortality in patients hospitalized for severe influenza. Early oseltamivir administration, which can only be given orally (or through a nasogastric tube), is thus recommended by the World Health Organization in patients hospitalized for severe influenza, including those requiring intensive care (ICU) admission. However, enteric absorption may be compromised in critically ill patients due to impaired gut function.
Read more
Hypothesis/Objective
The hypothese is that, in patients admitted for severe influenza, early (i.e., measured at the 48th hour of treatment initiation) oseltamivir carboxylate (OC) low plasma concentration would be: 1) associated with a poor prognosis; and 2) detectable by carrying out a paracetamol absorption test (PAT).
The main objective of the study is to determine the prognostic impact of early OC low plasma concentration in patients admitted to the intensive care unit (ICU) for severe influenza.
Primary outcome measure: Number of live ventilator-free days at 28-day in patients with versus without OC low plasma concentration.
Read the detailed description
Methods
Prospective cohort study conducted in 22 French intensive care units. Adult patients admitted to the ICU for severe influenza requiring invasive mechanical ventilation and treated with oseltamivir through a gastric tube for less than 24 hours will be included.
After inclusion, oseltamivir treatment will be continued through a gastric tube (75mg x 2 /day). After the 4th administration, plasma peak concentration of oseltamivir phosphate (OP) will be dosed at 60 minutes (CmaxOP) and plasma residual concentration of OC will be dosed at 12 hours (just before the 5th dose) (CresOC). A paracetamol absorption test will also be performed at the same time (consisting in the measurement of plasma paracetamol concentration 60 minutes after enteral loading with 1000 mg of paracetamol). CmaxOP and CresOC will also be measured at day 3 and 5 in order to realize pharmacokinetic analysis. Nasal swabs will be performed at inclusion (day 1) and day 5 for viral load quantification and viral strain sequencing (detection of the H275Y mutation). Clinical and biological variables will be collected from day 1 to day 90.
- Conditions
- Severe Influenza
- Being tested
- Absorption test
- Keywords
- Influenza, Intensive Care Unit, oseltamivir, paracetamol absorption test
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Absorption testOther
Paracetamol's administration (1 gram) - 48 hours after oseltamivir administration.
| Study group | Role | What they receive |
|---|---|---|
| Paracetamol absorption test | Experimental | Not described Receives: Other: Absorption test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live ventilator-free days (VFDs)
VFDs = 0 if subject dies within 28 days of mechanical ventilation. VFDs = 28 - x if successfully liberated from ventilation x days after initiation.
VFDs = 0 if the subject is mechanically ventilated for > 28 days.
Measured: Day 28
Secondary outcomes (10)
Diagnostic performance of the paracetamol absorption test (PAT)
Sensitivity = ability of PAT to correctly classify a patient as "having a low oseltamivir carboxylate (OC) concentration" = (true positive) / (true positive + false negative) Specificity = ability of PAT to correctly classify a patient as "not having a low oseltamivir carboxylate (OC) concentration" = (true negative) / (true negative + false positive) Positive predictive value (PPV) = percentage of patients with negative PAT who actually are "having a low oseltamivir carboxylate (OC) concentration"= (true positive) / (true positive + false positive) Negative predictive value (NPV) = percentage of patients with positive PAT who actually are not ""having a low oseltamivir carboxylate (OC) concentration" = (true negative) / (false negative + true negative) Positive Likelihood Ratio = Sensitivity / (1 - Specificity) Negative Likelihood Ratio = (1 - Sensitivity) / Specificity
Measured: 48 hours
Prevalence of patients with low plasma OC concentration
Measured: 48 hours
Independent variables present on admission associated with low plasma OC concentration
Measured: 48 hours
Prevalence of acquisition early OC concentration and viral clearance
Measured: 48 hours
Prevalence of acquisition of the oseltamivir resistance mutation (H275Y) in patients with versus without low plasma OC concentration.
Measured: 48 hours and day 5
Maximum oseltamivir carboxylate concentrations measurement
Measured: Days 2, 3 and 5
Maximum oseltamivir phosphate concentrations measurement
Measured: Days 2, 3 and 5
Residual oseltamivir carboxylate concentrations measurement
Measured: Days 2, 3 and 5
Residual oseltamivir phosphate concentrations measurement
Measured: Days 2, 3 and 5
Mortality
Measured: Days 28 and 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start1 Dec 2022 (estimated)
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe InfluenzaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 155 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne-Fleur Haudebourg, M.D, Study director, Assistance Publique Hôpitaux de Paris - CHU Henri Mondor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05375864
- Sponsor's protocol ID
- APHP210090
- Other IDs
- 2022-002377-28
- Acronym
- OPTIFLU
- Status last verified
- Nov 2022
- First submitted
- 9 May 2022
- Last updated
- 9 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: DATAS ARE OWNED BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prognostic Impact of Early Oseltamivir Carboxylate Low Plasma Concentration in Critically Ill Patients With Severe Influenza: a Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT05375864
- Acronym / sponsor ID
- OPTIFLU / APHP210090
- Conditions
- Severe Influenza
- Keywords
- Influenza, Intensive Care Unit, oseltamivir, paracetamol absorption test
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 155 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Dec 2022 (estimated)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Mar 2025 (estimated)
- First posted
- 17 May 2022 (actual)
- 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.
Introduction
Pandemic and seasonal influenza epidemics can be associated with a high degree of morbidity and mortality, especially in patients developing severe influenza pneumonitis with the acute respiratory distress syndrome (ARDS) or the less frequent fulminant myocarditis. Early administration (i.e. in the first 48 hours) of the neuraminidase inhibitor oseltamivir is associated with reduced mortality in patients hospitalized for severe influenza. Early oseltamivir administration, which can only be given orally (or through a nasogastric tube), is thus recommended by the World Health Organization in patients hospitalized for severe influenza, including those requiring intensive care (ICU) admission. However, enteric absorption may be compromised in critically ill patients due to impaired gut function.
Hypothesis/Objective
The hypothese is that, in patients admitted for severe influenza, early (i.e., measured at the 48th hour of treatment initiation) oseltamivir carboxylate (OC) low plasma concentration would be: 1) associated with a poor prognosis; and 2) detectable by carrying out a paracetamol absorption test (PAT).
The main objective of the study is to determine the prognostic impact of early OC low plasma concentration in patients admitted to the intensive care unit (ICU) for severe influenza.
Primary outcome measure: Number of live ventilator-free days at 28-day in patients with versus without OC low plasma concentration.
Detailed description
Methods
Prospective cohort study conducted in 22 French intensive care units. Adult patients admitted to the ICU for severe influenza requiring invasive mechanical ventilation and treated with oseltamivir through a gastric tube for less than 24 hours will be included.
After inclusion, oseltamivir treatment will be continued through a gastric tube (75mg x 2 /day). After the 4th administration, plasma peak concentration of oseltamivir phosphate (OP) will be dosed at 60 minutes (CmaxOP) and plasma residual concentration of OC will be dosed at 12 hours (just before the 5th dose) (CresOC). A paracetamol absorption test will also be performed at the same time (consisting in the measurement of plasma paracetamol concentration 60 minutes after enteral loading with 1000 mg of paracetamol). CmaxOP and CresOC will also be measured at day 3 and 5 in order to realize pharmacokinetic analysis. Nasal swabs will be performed at inclusion (day 1) and day 5 for viral load quantification and viral strain sequencing (detection of the H275Y mutation). Clinical and biological variables will be collected from day 1 to day 90.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Paracetamol absorption test | Experimental | Other: Absorption test |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients
- Confirmed severe influenza infection requiring intensive care with tracheal intubation for invasive mechanical ventilation (influenza ARDS with or without bacterial co-infection, cardiorespiratory decompensation of influenza origin, influenza myocarditis)
- Oseltamivir treatment administered through a gastric tube initiated since less than 24 hours (i.e. maximum two doses administered)
- Affiliation to a social security system or beneficiary (excluding AME)
- Written consent obtained (or under emergency procedures)
Key exclusion criteria (11 listed)
- Pregnancy or breastfeeding women
- Weight less than 40 kg
- Zanamivir or other antiviral effective treatment received for more than 24 hours
- Other respiratory virus infection (including SARS-CoV-2)
- Contra-indication to esophageal tube insertion or use
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 |
|---|---|---|
| Absorption testParacetamol's administration (1 gram) - 48 hours after oseltamivir administration. | Other | Paracetamol absorption test |
Primary outcome
Live ventilator-free days (VFDs)
Time frame: Day 28
VFDs = 0 if subject dies within 28 days of mechanical ventilation. VFDs = 28 - x if successfully liberated from ventilation x days after initiation. VFDs = 0 if the subject is mechanically ventilated for > 28 days.
10 secondary outcomes
Diagnostic performance of the paracetamol absorption test (PAT)
Time frame: 48 hours
Prevalence of patients with low plasma OC concentration
Time frame: 48 hours
Independent variables present on admission associated with low plasma OC concentration
Time frame: 48 hours
Prevalence of acquisition early OC concentration and viral clearance
Time frame: 48 hours
Prevalence of acquisition of the oseltamivir resistance mutation (H275Y) in patients with versus without low plasma OC concentration.
Time frame: 48 hours and day 5
Maximum oseltamivir carboxylate concentrations measurement
Time frame: Days 2, 3 and 5
Maximum oseltamivir phosphate concentrations measurement
Time frame: Days 2, 3 and 5
Residual oseltamivir carboxylate concentrations measurement
Time frame: Days 2, 3 and 5
Residual oseltamivir phosphate concentrations measurement
Time frame: Days 2, 3 and 5
Mortality
Time frame: Days 28 and 90
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2022.
- Individual participant dataSharing planned: No. DATAS ARE OWNED BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
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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.
Anne-Fleur Haudebourg, M.D study director
Assistance Publique Hôpitaux de Paris - CHU Henri Mondor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Absorption test in people with Severe Influenza, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 5 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 9 Dec 2022. 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 France. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anne-Fleur Haudebourg, M.D (01 45 17 85 06 ext. +33, annefleur.maignant@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live ventilator-free days (VFDs) (time frame: Day 28). 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 9 Dec 2022.