AMIKACIN SULFATE for Ventilator-associated pneumonia (Gram-negative)

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years old\n- Circulatory assistance by ECMO veno-arterial for at least 24 hours prior to documentation of pneumonia\n- Invasive mechanical ventilation\n- Diagnostic suspicion of pneumonia based on suggestive criteria (presence of at least 2 of the following criteria): fever >38. 5°C, hyperleukocytosis >11 × 109 l-1 or leukopenia <4 × 109 l-1, purulent tracheobronchial secretions, altered oxygenation with the need to increase FiO2 on the ECMO or ventilator for the same SaO2 or PaO2 target, new or persistent pulmonary infiltrate(s) on chest X-ray in bed, or an image suggestive of pneumonia on a chest CT scan, or consolidation of an appearance suggestive of an infectious origin on lung ultrasound\n- Microbiological confirmation of gram-negative ventilator-associated pneumonia by quantitative culture on bronchoalveolar lavage (BAL, significance threshold > 104 CFU/ml) or protected distal sampling (PDP, significance threshold > 103 CFU/ml)\n- Probabilistic antibiotic therapy with piperacillin - tazobactam\n- Informed consent obtained from the patient or his/her trusted support person if unable to consent at the time of inclusion, or inclusion procedure in an emergency situation\n- Patient affiliated to a social security scheme (excluding AME)"}

Exclusion criteria

• {"criterion_text":"- Known allergy to amikacin or another aminoglycoside\n- Patient moribund or with a high probability of death within 48 hours\n- Patient under legal protection (curatorship, guardianship or safeguard of justice)\n- Participating in another interventional clinical trial or within the exclusion period at the end of a previous study\n- Contraindications to the administration of amikacin\n- Contraindications to nebulisation\n- Intravenous antibiotic therapy started more than 72 hours before administration of the first dose of study treatment\n- Probabilistic venous antibiotic therapy other than piperacillin-tazobactam\n- Administration of inhaled antibiotics in the 7 days prior to inclusion\n- Positive pregnancy test for women of childbearing potential\n- Presence of HIV infection with CD4 count <200 cells/mm3 or fungal lung infection or pulmonary abscess or empyema\n- Presence of renal insufficiency with creatinine clearance < 15 ml/min, with the exception of patients receiving continuous renal purification or daily haemodialysis sessions as part of their intensive care treatment"}

Primary endpoints

• {"endpoint_text":"- Bacterial eradication rate, defined as absence of germs on direct examination and negative culture of a tracheal aspirate taken on day 5 (D5) after randomisation and at least 12 hours after the last administration of inhaled amikacin","definition_or_measurement_approach":"Defined as absence of germs on direct examination and negative culture of a tracheal aspirate taken on day 5 (D5) after randomisation and at least 12 hours after the last administration of inhaled amikacin"}

Secondary endpoints

• {"endpoint_text":"- Clinical cure rate, defined as the disappearance of clinical signs suggestive of pneumonia, biological inflammatory syndrome, and correction of haematosis disorders, at D5","definition_or_measurement_approach":"Defined as disappearance of clinical signs suggestive of pneumonia, resolution of biological inflammatory syndrome, and correction of haematosis disorders at Day 5"}
• {"endpoint_text":"- Pneumonia persistence rate defined as the presence of the pathogen identified at a significant level on culture of tracheal aspirate at D5","definition_or_measurement_approach":"Presence of the pathogen identified at a significant level on culture of tracheal aspirate at Day 5"}
• {"endpoint_text":"- Difference between CPIS score at D5 and CPIS score at randomization","definition_or_measurement_approach":"Difference in Clinical Pulmonary Infection Score (CPIS) between randomisation and Day 5"}
• {"endpoint_text":"- Difference between ultrasound lung ventilation score at D5 and lung ventilation score at randomization","definition_or_measurement_approach":"Difference in lung aeration assessment score by lung ultrasound between randomisation and Day 5"}
• {"endpoint_text":"- Quantifying and analysing adverse events","definition_or_measurement_approach":"Collection, quantification and analysis of adverse events and serious adverse events as reported during the study"}
• {"endpoint_text":"- Pharmacokinetic analysis of plasma concentrations of piperacillin-tazobactam","definition_or_measurement_approach":"Pharmacokinetic analysis of measured plasma concentrations of piperacillin-tazobactam"}
• {"endpoint_text":"- Measurement of the ratio of penetration into alveolar fluid (AUC alveolar fluid/AUC plasma) of piperacillin-tazobactam in patients undergoing VA-ECMO after 2 days of intravenous antibiotic therapy","definition_or_measurement_approach":"Measurement of AUC in alveolar fluid and plasma to calculate alveolar fluid AUC / plasma AUC ratio after 2 days of IV antibiotic therapy"}

France

Earliest CTIS Part Ii Submission Date

17-05-2024

Latest Decision Or Authorization Date

26-03-2026

Processing Time Days

678

Number Of Sites

2

Number Of Participants

26

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France