Clinical trial NCT06602557: " a Randomized Pilot Study of the Benefit of Nebulized Amikacin in the Treatment of Gram-negative Bacillus Pneumonia Acquired During Mechanical Ventilation in Patients Receiving Extracorporeal Membrane Veno-arterial Oxygenation (ECMO-VA)."
Official title: " a Randomized Pilot Study of the Benefit of Nebulized Amikacin in the Treatment of Gram-negative Bacillus Pneumonia Acquired During Mechanical Ventilation in Patients Receiving Extracorporeal Membrane Veno-arterial Oxygenation (ECMO-VA). "
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Pneumonia, Bacterial
Extracorporeal Membrane Oxygenation
Keywords: ECMO
Hospital acquired pneumonia
Antibiotic nebulization
Pharmacokinetic
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pneumonia are the most frequent infectious complication in patients on Extracorporeal Membrane Oxygenation Veno-arterial (ECMO-VA), with a treatment failure rate of around 40%, even though antibiotic therapy is tailored to the germs identified. One hypothesis to explain this particularly high failure rate is the reduced pulmonary blood flow associated with ECMO offloading of the heart. Although there are no data to date on the pulmonary penetration of antibiotics in patients undergoing VA-ECMO, this phenomenon of pulmonary hypoperfusion could contribute to altering the alveolocapillary diffusion of antibiotics, thereby reducing their concentration in the pulmonary parenchyma.

Our hypothesis is that amikacin nebulization could increase bacterial clearance and, ultimately, limit treatment failure or recurrence of gram-negative bacilli (GNB) pneumonia in patients undergoing VA-ECMO.


Eligibility criteria: Inclusion Criteria:

1. Patient 18 years or older
2. Circulatory assistance by veno-arterial ECMO for at least 24 hours prior to documentation of pneumonia
3. Invasive mechanical ventilation
4. Diagnostic suspicion of pneumonia based on evocative criteria (presence of at least 2 of the following criteria): fever (superior to 38. 5°C), hypothermia (inferior to 36.0°C), hyperleukocytosis (superior to 11 × 10\^9 l-1) or leukopenia (inferior to 4 × 10\^9 l-1), purulent tracheobronchial secretions, altered oxygenation with need to increase FiO2 on ECMO or ventilator for the same SaO2 or PaO2 target, new or persistent pulmonary infiltrate(s) on chest x-ray in bed, or image suggestive of pneumonia on chest CT, or consolidation of appearance suggestive of an infectious origin on pulmonary ultrasound.
5. And microbiological confirmation of Gram-negative ventilator-associated pneumonia by quantitative culture on bronchoalveolar lavage (BAL, significance threshold superior to 10\^4 CFU/ml) or protected distal sampling (PDP, significance threshold superior to 10\^3 CFU/ml).
6. Probabilistic antibiotic therapy with piperacillin - tazobactam
7. Informed consent obtained from the patient or trusted support person if unable to consent at the time of inclusion, or inclusion procedure in emergency situations.
8. Patient affiliated to social security (excluding AME)

Exclusion Criteria:

1. Known allergy to amikacin or another aminoglycoside or to an auxiliary drug or to any of their excipients.
2. Contraindication to the administration of amikacin or its excipients listed in the summary of product characteristics.
3. Contraindication to the administration of an auxiliary drug or to one of its excipients listed in the summary of product characteristics.
4. Contraindications to nebulization
5. Intravenous antibiotic therapy started more than 72 hours before randomization
6. Probabilistic venous antibiotic therapy other than piperacillin - tazobactam
7. Administration of inhaled antibiotics within 7 days prior to inclusion
8. Positive pregnancy test for women of childbearing potential
9. Presence of HIV infection with CD4 count inferior to 200 cells/mm3 or fungal lung infection or pulmonary abscess or empyema
10. Presence of renal insufficiency with creatinine clearance inferior to 15 ml/min, with the exception of patients receiving continuous renal purification or daily hemodialysis sessions as part of their intensive care unit management.
11. Patent moribund (SAPS II superior to 75) or high probability of death within 48 hours
12. Patient under legal protection (curatorship, guardianship or safeguard of justice)
13. Participating in another interventional clinical trial or within the exclusion period at the end of a previous study.

Primary outcomes:
measure: Bacterial eradication rate
timeFrame: Day 5
Secondary outcomes:
measure: Clinical cure rate
timeFrame: Day 5
measure: Pneumonia persistence rate
timeFrame: Day 5
measure: Change in clinical pulmonary infection score (CPIS)
timeFrame: Day 0 to Day 5
measure: Change in pulmonary aeration score
timeFrame: Day 0 to Day 5
measure: Adverse events
timeFrame: Day 0 to Day 5
measure: Pharmacokinetic analysis of piperacillin tazobactam
timeFrame: Day 1
measure: Alveolar fluid penetration ratio of piperacillin-tazobactam
timeFrame: Day 1
measure: Pharmacokinetic analysis of Amikacin
timeFrame: Day 1 to Day 5
measure: Alveolar fluid concentration of Amikacin
timeFrame: Day 1
Other outcomes:
Locations:
Study officials:
References: