" 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)."

NCT06602557 | Not Yet Recruiting Phase 2

• 1 other identifier: NAVAP-ECMO
• Study Type: interventional
• Target: 26
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pneumonia, Bacterial; Extracorporeal Membrane Oxygenation

Keywords

ECMO; Hospital acquired pneumonia; Antibiotic nebulization; Pharmacokinetic

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• Clinical cure rate

  Day 5

• Pneumonia persistence rate

  Day 5

• Change in clinical pulmonary infection score (CPIS)

  Day 0 to Day 5

• Change in pulmonary aeration score

  Day 0 to Day 5

• Adverse events

  Day 0 to Day 5

Study Arms (2)

Amikacine nebulization associated with Standard of care

EXPERIMENTAL

Drug: Amikacin

Standard of care

ACTIVE COMPARATOR

Drug: Standard of care

Interventions

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.

Amikacine nebulization associated with Standard of care

Standard of care DRUG

Patients included in the standard of care group will not receive any nebulization. They will receive Standard care alone.

Standard of care

Eligibility Criteria

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

You may qualify if:

• Patient 18 years or older
• Circulatory assistance by veno-arterial ECMO for at least 24 hours prior to documentation of pneumonia
• Invasive mechanical ventilation
• 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.
• 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).
• Probabilistic antibiotic therapy with piperacillin - tazobactam
• Patient affiliated to social security (excluding AME)

You may not qualify if:

• Known allergy to amikacin or another aminoglycoside or to an auxiliary drug or to any of their excipients.
• Contraindication to the administration of amikacin or its excipients listed in the summary of product characteristics.
• Contraindication to the administration of an auxiliary drug or to one of its excipients listed in the summary of product characteristics.
• Contraindications to nebulization
• Intravenous antibiotic therapy started more than 72 hours before randomization
• Probabilistic venous antibiotic therapy other than piperacillin - tazobactam
• Positive pregnancy test for women of childbearing potential
• Presence of HIV infection with CD4 count inferior to 200 cells/mm3 or fungal lung infection or pulmonary abscess or empyema
• 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.
• Patent moribund (SAPS II superior to 75) or high probability of death within 48 hours
• Patient under legal protection (curatorship, guardianship or safeguard of justice)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Pneumonia, Bacterial; Healthcare-Associated Pneumonia

Interventions

Amikacin; Standard of Care

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Kanamycin; Aminoglycosides; Glycosides; Carbohydrates; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: September 19, 2024
• Study Start: November 15, 2024
• Primary Completion: May 15, 2025
• Study Completion (Estimated): May 15, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.
• Access Criteria: Researchers who provide a methodologically sound proposal.