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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Amikacine nebulization associated with Standard of care | Experimental |
| |
| Standard of care | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amikacin | Drug | Patients included in the inhaled amikacin group will receive inhaled antibiotic therapy by nebulization of amikacin at a dose of 25 mg/kg in 1 daily dose (+/- 3 hours apart), within 6 hours of randomization and for a total duration of 5 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Bacterial eradication rate | Bacterial eradication rate, defined as absence of germs on direct examination and negative culture of a tracheal aspirate taken on day 5 (D5) after randomization and at least 12 hours after the last administration of inhaled amikacin. | Day 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical cure rate | Clinical cure rate, defined as disappearance of clinical signs suggestive of pneumonia, biological inflammatory syndrome and correction of haematosis disorders, at D5. | Day 5 |
| Pneumonia persistence rate |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pauline DUREAU, MD, PhD | Contact | 01 84 82 76 89 | pauline.dureau@aphp.fr | |
| Alexis CALOC, Clinical project manager | Contact | 01 42 16 24 37 | alexis.caloc@aphp.fr |
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The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.
Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.
Researchers who provide a methodologically sound proposal.
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| Standard of care | Drug | Patients included in the standard of care group will not receive any nebulization. They will receive Standard care alone. |
|
Pneumonia persistence rate defined as the presence of the pathogen identified at a significant level on culture of tracheal aspirate at D5.
| Day 5 |
| Change in clinical pulmonary infection score (CPIS) | Difference between CPIS score at D5 and CPIS score at randomization. | Day 0 to Day 5 |
| Change in pulmonary aeration score | Difference between ultrasound pulmonary aeration score at D5 and pulmonary aeration score at randomization. | Day 0 to Day 5 |
| Adverse events | Quantifying and analysing adverse events and serious adverse events | Day 0 to Day 5 |
| Pharmacokinetic analysis of piperacillin tazobactam | Pharmacokinetic analysis of plasma concentrations of the piperacillin - tazobactam combination | Day 1 |
| Alveolar fluid penetration ratio of piperacillin-tazobactam | Measurement of the alveolar fluid penetration ratio (AUC* alveolar fluid / AUC plasma) of piperacillin-tazobactam in patients on ECMO-VA after 2 days of intravenous antibiotic administration. *Area Under the Curve | Day 1 |
| Pharmacokinetic analysis of Amikacin | Measurement of the plasma concentration of Amikacin in patients on ECMO-VA in the treatment group between D1 and D5. | Day 1 to Day 5 |
| Alveolar fluid concentration of Amikacin | Measurement of the alveolar fluid concentration of Amikacin in patients on ECMO-VA after one nebulization in the treatment group (after 24 hours of treatment) | Day 1 |
| ID | Term |
|---|---|
| D018410 | Pneumonia, Bacterial |
| D000077299 | Healthcare-Associated Pneumonia |
| ID | Term |
|---|---|
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D003428 | Cross Infection |
| D007049 | Iatrogenic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000583 | Amikacin |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D007612 | Kanamycin |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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