Clinical trial • Phase III • Infectious Disease
OSELTAMIVIR for Severe influenza
Phase III trial of OSELTAMIVIR for Severe influenza. None/Not specified-controlled. 155 participants.
Overview
- Trial Therapeutic Area
- Infectious Disease
- Trial Disease
- Severe influenza
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 12-09-2024
- First CTIS Authorization Date
- 10-10-2024
Trial design
None/Not specified-controlled Phase III trial across 28 sites in France.
- Comparator
- None/Not specified
- Target Sample Size
- 155
- Trial Duration For Participant
- 90
Eligibility
Recruits 155 Vulnerable population considerations: the trial includes provisions for consent by the patient or, if the patient is unable, by a trusted support person or an informed family member who has given written consent; inclusion according to emergency procedures is allowed. Patients deprived of liberty or under legal protection (guardianship or curatorship) are excluded. For patients not included in emergency situations, non-French-speaking patients who are unable to understand or refuse to sign informed consent are excluded. Proxy/guardian consent procedures and proxy information/ICF documents are present in the trial documentation..
- Pregnancy Exclusion
- Pregnant or breastfeeding woman
- Vulnerable Population
- Vulnerable population considerations: the trial includes provisions for consent by the patient or, if the patient is unable, by a trusted support person or an informed family member who has given written consent; inclusion according to emergency procedures is allowed. Patients deprived of liberty or under legal protection (guardianship or curatorship) are excluded. For patients not included in emergency situations, non-French-speaking patients who are unable to understand or refuse to sign informed consent are excluded. Proxy/guardian consent procedures and proxy information/ICF documents are present in the trial documentation.
Inclusion criteria
- {"criterion_text":"- Patients over 18 years of age\n- 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)\n- Oseltamivir treatment administered through a gastric tube initiated since less than 24 hours (i.e. maximum two doses administered)\n- Affiliation to a social security scheme, beneficiary or beneficiary entitled (excluding AME)\n- Patient or, by default, a trusted support person or, by default, an informed family member who has given written consent or patient who has been included in emergency procedures."}
Exclusion criteria
- {"criterion_text":"- Pregnant or breastfeeding woman\n- Patient deprived of liberty or under legal protection (guardianship or curatorship)\n- For patients not included in emergency situations: Inability, according to the investigator, to understand or refusal to sign the informed consent to participate in the study (non-French-speaking patient).\n- Weight less than 40 kg\n- Previous treatment with Zanamivir or other antiviral treatment active against influenza virus for more than 24 hours\n- Co-infection with another respiratory virus (including SARS CoV-2)\n- Administration of medication via nasogastric tube impossible\n- Current participation in a therapeutic interventional trial or be in the exclusion period at the end of a clinical trial (drugs that may interact with paracetamol or oseltamivir)\n- Patient benefiting from AME (Aide Médicale d'Etat)"}
Endpoints
Primary endpoints
- {"endpoint_text":"- The primary endpoint is the number of days alive without invasive mechanical ventilation at D28.","definition_or_measurement_approach":"Number of days alive and free from invasive mechanical ventilation within 28 days (assessed at day 28)."}
Secondary endpoints
- {"endpoint_text":"- Diagnostic performance of the paracetamol absorption test (sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios) performed at H48 for the diagnosis of plasma oseltamivir underdosing.\n- Prevalence of patients with low plasma OC concentration\n- Plasma OC underdosage at H48 (dependent variable); the independent variables are the clinical and biological data present on admission, which will be studied as prognostic factors for OC underdosage using univariate and multivariate logistic regression models.\n- Viral clearance, calculated from nasopharyngeal viral load measurements taken on D1 (initial influenza diagnostic test) and D5. The association between viral clearance and plasma OC concentration at H48 will be assessed.\n- Prevalence of acquisition of the H275Y oseltamivir resistance mutation (investigated by PCR and high-throughput sequencing).\n- Measurements of Cmax and Residual OC and oseltamivir phosphate (OP, inactive prodrug) at D2, D3 and D5\n- Mortality at D28 and D90 in patients under-dosed in OC at 48h of treatment initiation and in patients not under-dosed","definition_or_measurement_approach":"Diagnostic performance: sensitivity, specificity, predictive values and likelihood ratios of paracetamol absorption test at H48 for diagnosing plasma OC underdosing. Prevalence: proportion of patients with low plasma OC concentration at H48. OC underdosage prognostic factors: studied via univariate and multivariate logistic regression using clinical and biological admission data. Viral clearance: calculated from nasopharyngeal viral load at D1 and D5 and associated with plasma OC at H48. H275Y mutation: detected by PCR and high-throughput sequencing. Pharmacokinetics: Cmax and residual concentrations of OC and OP measured at D2, D3 and D5. Mortality: all-cause mortality assessed at day 28 and day 90."}
Recruitment
- Planned Sample Size
- 155
- Recruitment Window Months
- 27
- Consent Approach
- Informed consent is obtained from the patient when possible. If the patient cannot consent, written consent may be provided by a trusted support person or, by default, an informed family member. Inclusion under emergency procedures is allowed. Proxy-specific information and ICF documents are included in trial documentation. For non-emergency inclusions, non-French-speaking patients who cannot understand or refuse to sign the informed consent are excluded.
Geography
- Total Number Of Sites
- 28
- Total Number Of Participants
- 155
France
- Earliest CTIS Part Ii Submission Date
- 03-10-2024
- Latest Decision Or Authorization Date
- 08-08-2025
- Processing Time Days
- 309
- Number Of Sites
- 28
- Number Of Participants
- 155
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation Intensive Réanimation
- Principal Investigator Name
- Anne-Fleur HAUDEBOURG
- Principal Investigator Email
- annefleur.maignant@aphp.fr
- Contact Person Name
- Anne-Fleur HAUDEBOURG
- Contact Person Email
- annefleur.maignant@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Médecine intensive et réanimation infectieuse
- Principal Investigator Name
- Romain SONNEVILLE
- Principal Investigator Email
- romain.sonneville@aphp.fr
- Contact Person Name
- Romain SONNEVILLE
- Contact Person Email
- romain.sonneville@aphp.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Réanimation Médicale
- Principal Investigator Name
- Jean-Christophe RICHARD
- Principal Investigator Email
- j-christophe.richard@chu-lyon.fr
- Contact Person Name
- Jean-Christophe RICHARD
- Contact Person Email
- j-christophe.richard@chu-lyon.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Gaëtan BEDUNEAU
- Principal Investigator Email
- gaetan.beduneau@chu-rouen.fr
- Contact Person Name
- Gaëtan BEDUNEAU
- Contact Person Email
- gaetan.beduneau@chu-rouen.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Réanimation médicale
- Principal Investigator Name
- Pauline GUILLOT
- Principal Investigator Email
- pauline.guillot@chu-rennes.fr
- Contact Person Name
- Pauline GUILLOT
- Contact Person Email
- pauline.guillot@chu-rennes.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Martin COUR
- Principal Investigator Email
- martin.cour@chu-lyon.fr
- Contact Person Name
- Martin COUR
- Contact Person Email
- martin.cour@chu-lyon.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Arnaud THILLE
- Principal Investigator Email
- arnaud.thille@chu-poitiers.fr
- Contact Person Name
- Arnaud THILLE
- Contact Person Email
- arnaud.thille@chu-poitiers.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation médicale
- Principal Investigator Name
- Charles-Edouard LUYT
- Principal Investigator Email
- charles-edouard.luyt@aphp.fr
- Contact Person Name
- Charles-Edouard LUYT
- Contact Person Email
- charles-edouard.luyt@aphp.fr
- Site Name
- Centre Hospitalier Et Universitaire De Limoges
- Department Name
- Réanimation Polyvalente
- Principal Investigator Name
- Thomas DAIX
- Principal Investigator Email
- thomas.Daix@chu-limoges.fr
- Contact Person Name
- Thomas DAIX
- Contact Person Email
- thomas.Daix@chu-limoges.fr
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Antoine GUILLON
- Principal Investigator Email
- antoine.guillon@univ-tours.fr
- Contact Person Name
- Antoine GUILLON
- Contact Person Email
- antoine.guillon@univ-tours.fr
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Julie HELMS
- Principal Investigator Email
- julie.helms@chru-strasbourg.fr
- Contact Person Name
- Julie HELMS
- Contact Person Email
- julie.helms@chru-strasbourg.fr
- Site Name
- Groupe Hospitalier Du Sud Ile De France
- Department Name
- Médecine Intensive
- Principal Investigator Name
- Sébastien JOCHMANS
- Principal Investigator Email
- sebastien.jochmans@ghsif.fr
- Contact Person Name
- Sébastien JOCHMANS
- Contact Person Email
- sebastien.jochmans@ghsif.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Médecine intensive -réanimation
- Principal Investigator Name
- Tài Olivier PHAM
- Principal Investigator Email
- tai.pham@aphp.fr
- Contact Person Name
- Tài Olivier PHAM
- Contact Person Email
- tai.pham@aphp.fr
- Site Name
- Centre Hospitalier Universitaire Grenoble Alpes
- Department Name
- Réanimation Médicale
- Principal Investigator Name
- Florian SIGAUD
- Principal Investigator Email
- fsigaud@chu-grenoble.fr
- Contact Person Name
- Florian SIGAUD
- Contact Person Email
- fsigaud@chu-grenoble.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation Médicale et Toxicologique
- Principal Investigator Name
- Bruno MEGARBANE
- Principal Investigator Email
- bruno.megarbane@aphp.fr
- Contact Person Name
- Bruno MEGARBANE
- Contact Person Email
- bruno.megarbane@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Réanimation
- Principal Investigator Name
- Saadala NSEIR
- Principal Investigator Email
- saadalla.nseir@chru-lille.fr
- Contact Person Name
- Saadala NSEIR
- Contact Person Email
- saadalla.nseir@chru-lille.fr
- Site Name
- Centre Hospitalier Universitaire D Orleans
- Department Name
- Hôpital La Source -Réanimation Intensive Réanimation
- Principal Investigator Name
- François BARBIER
- Principal Investigator Email
- francois.barbier@chr-orleans.fr
- Contact Person Name
- François BARBIER
- Contact Person Email
- francois.barbier@chr-orleans.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation Médico-chirurgicale
- Principal Investigator Name
- Damien ROUX
- Principal Investigator Email
- damien.roux@aphp.fr
- Contact Person Name
- Damien ROUX
- Contact Person Email
- damien.roux@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Médecine Intensive Réanimation et Pneumologie
- Principal Investigator Name
- Julien MAYAUX
- Principal Investigator Email
- julien.mayaux@aphp.fr
- Contact Person Name
- Julien MAYAUX
- Contact Person Email
- julien.mayaux@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation Médico-chirurgicale
- Principal Investigator Name
- Antoine VIEILLARD-BARON
- Principal Investigator Email
- antoine.vieillard-baron@aphp.fr
- Contact Person Name
- Antoine VIEILLARD-BARON
- Contact Person Email
- antoine.vieillard-baron@aphp.fr
- Site Name
- Centre Hospital Region Metz Thionville
- Department Name
- Réanimation polyvalente de Mercy
- Principal Investigator Name
- Guillaume LOUIS
- Principal Investigator Email
- guillaume.louis@chr-metz-thionville.fr
- Contact Person Name
- Guillaume LOUIS
- Contact Person Email
- guillaume.louis@chr-metz-thionville.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Frédéric PENE
- Principal Investigator Email
- frederic.pene@aphp.fr
- Contact Person Name
- Frédéric PENE
- Contact Person Email
- frederic.pene@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation Intensive Réanimation
- Principal Investigator Name
- Muriel FARTOUKH
- Principal Investigator Email
- muriel.fartoukh@aphp.fr
- Contact Person Name
- Muriel FARTOUKH
- Contact Person Email
- muriel.fartoukh@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation médico-chirurgicale
- Principal Investigator Name
- Stéphane GAUDRY
- Principal Investigator Email
- stephane.gaudry@aphp.fr
- Contact Person Name
- Stéphane GAUDRY
- Contact Person Email
- stephane.gaudry@aphp.fr
- Site Name
- Centre Hospitalier Victor Dupouy
- Department Name
- Réanimation Polyvalente
- Principal Investigator Name
- Damien CONTOU
- Principal Investigator Email
- damien.contou@ch-argenteuil.fr
- Contact Person Name
- Damien CONTOU
- Contact Person Email
- damien.contou@ch-argenteuil.fr
- Site Name
- Centre Hospitalier Universitaire De Saint Etienne
- Department Name
- Réanimation Médicale
- Principal Investigator Name
- Guillaume THIERY
- Principal Investigator Email
- guillaume.thiery@chu-st-etienne.fr
- Contact Person Name
- Guillaume THIERY
- Contact Person Email
- guillaume.thiery@chu-st-etienne.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation Médicale
- Principal Investigator Name
- Lara ZAFRANI
- Principal Investigator Email
- lara.zafrani@aphp.fr
- Contact Person Name
- Lara ZAFRANI
- Contact Person Email
- lara.zafrani@aphp.fr
- Site Name
- Centre Hospitalier De Versailles
- Department Name
- Réanimation médico-chirurgicale
- Principal Investigator Name
- Alexis FERRE
- Principal Investigator Email
- aferre@ch-versailles.fr
- Contact Person Name
- Alexis FERRE
- Contact Person Email
- aferre@ch-versailles.fr
Sponsor
Primary sponsor
- Full Name
- Assistance Publique Hopitaux De Paris
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Third parties
- {"country":"","full_name":"French Ministry of Health PHRC Interrégional 2020","duties_or_roles":"Source of monetary support","organisation_type":""}
Investigational products
- Investigational Product Name
- Tamiflu 75 mg hard capsules
- Active Substance
- OSELTAMIVIR
- Modality
- Small molecule
- Routes Of Administration
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Route
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Authorisation Status
- Authorised
- Maximum Dose
- 150 mg per day
- Investigational Product Name
- DOLIPRANE 1000 mg, poudre pour solution buvable en sachet-dose
- Active Substance
- PARACETAMOL
- Modality
- Small molecule
- Routes Of Administration
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Route
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Authorisation Status
- Authorised
- Maximum Dose
- 1000 mg per day
Related trials
Other published trials that may interest you.
- Conditioned medium from a co-culture of M2-macrophages and fat-derived mesenchymal cells for Acute respiratory distress syndrome (ARDS) | SARS-CoV-2 infection | Influenza A infection | Influenza B infection | Respiratory syncytial virus (RSV) infection
- ACICLOVIR for Recurrent herpes labialis | Herpes simplex labialis
- AMIKACIN SULFATE for Sepsis | Neutropenia
- LENACAPAVIR, ISLATRAVIR for HIV-1 infection
- piperacillin sodium, tazobactam sodium for Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae severe infection