Early Oseltamivir Carboxylate Low Plasma Concentration in Patients Admitted to Intensive Care for Severe Influenza

NCT05375864 | Unknown DMC

• 2 other identifiers: APHP2100902022-002377-28
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Severe Influenza

Keywords

Influenza; Intensive Care Unit; oseltamivir; paracetamol absorption test

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 28

Secondary Outcomes (10)

• Diagnostic performance of the paracetamol absorption test (PAT)

  48 hours

• Prevalence of patients with low plasma OC concentration

  48 hours

• Independent variables present on admission associated with low plasma OC concentration

  48 hours

• Prevalence of acquisition early OC concentration and viral clearance

  48 hours

• Prevalence of acquisition of the oseltamivir resistance mutation (H275Y) in patients with versus without low plasma OC concentration.

  48 hours and day 5

Study Arms (1)

Paracetamol absorption test

EXPERIMENTAL

Other: Absorption test

Interventions

Absorption test OTHER

Paracetamol's administration (1 gram) - 48 hours after oseltamivir administration.

Paracetamol absorption test

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Anne-Fleur Haudebourg

Créteil, 94010, France

Location

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Anne-Fleur Haudebourg, M.D

  Assistance Publique Hôpitaux de Paris - CHU Henri Mondor

  STUDY DIRECTOR

Central Study Contacts

Anne-Fleur Haudebourg, M.D

CONTACT

01 45 17 85 06; annefleur.maignant@aphp.fr

Nicolas de Prost, M.D., Ph.D

CONTACT

01 45 17 86 37; nicolas.de-prost@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: 1. Laboratory staff assessing the paracetamol assay will be blinded to the results of the plasma oseltamivir assay and vice versa. 2. The investigators will be blinded to the assays.
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2022
• First Posted: May 17, 2022
• Study Start: December 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: March 1, 2025
• Last Updated: December 9, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)