Pulmonary Diffusion of Antibiotics in Patients Admitted for ARDS Following SARS-CoV-2 Pneumonia

ARDS Clinical Trial

— ATB-COVID  

Official title:

Pulmonary Diffusion of Antibiotics During Mechanically Ventilated Pneumonia in Patients Admitted for ARDS Following SARS-CoV-2 Pneumonia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05464680
• Other study ID #: RCAPHM21_0415
• Secondary ID: ID-RCB
• Status: Recruiting
• Phase: N/A
• Start date: November 24, 2022
• Est. completion date: February 23, 2025

Study information

• Verified date: July 2023
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Sami Hraiech
• Phone: 04 91 96 58 43
• Email: sami.hraiech[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients on mechanical ventilation (MV) following SARS-CoV-2 pneumonia frequently develop ventilator-associated pneumonia (VAP). The incidence of MVAP during SARS-CoV-2 infections ranges from 50 to nearly 90%. In addition, up to 80% of recurrences of VAP (a new episode, most often attributable to the same bacteria) have been described, reflecting the failure of the initial antibiotic therapy. This incidence is much higher than that described for other etiologies of acute respiratory distress syndrome (ARDS). The investigators hypothesize that during VAP, there is an alteration of the diffusion of intravenous antibiotics in the lung parenchyma in COVID-19 patients in relation to several factors characteristic of SARS-CoV-2 infection. This altered diffusion may explain the high number of recurrences of MVAP compared to non-COVID-19 patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 23, 2025
• Est. primary completion date: November 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Patient over 18 years of age 2. Patient has given consent or consent obtained from the trusted person if the patient is not capable of consenting, after informed consent.

3. Patient with ARDS 4. Patient requiring MV for ARDS (as defined by Berlin (15)), regardless of etiology (COVID-19 or other cause of ARDS) 5. Patient with suspected 1st episode of ARDS for which microbiological sampling is performed (bronchial aspiration, protected distal sampling (PDS), bronchoalveolar lavage (BAL)) 6. Patients who have received probabilistic antibiotic therapy within 24 hours of the microbiological sample, including piperacillin-tazobactam (PIP-TAZ) administered according to current recommendations.

7. Patient who is a beneficiary of or affiliated to a social security system

Exclusion Criteria:

1. Patients for whom PIP-TAZ is administered as a discontinuous infusion.

2. Contraindication to the realization of a mini-LBA: patient whose respiratory state is too precarious for the realization of a mini-LBA for intra pulmonary antibiotics dosage (SpO2<94% under FiO2 100% under VM), presence of a non drained pneumothorax, bronchial prosthesis, recent bronchial suture

3. Patient with a second episode of PAVM.

4. Patients with KDIGO stage = 3 renal failure or extra-renal replacement therapy (creatinine measurement on the day of inclusion, performed as part of routine care).

5. Patient on ExtraCorporeal Membrane Oxygenation (ECMO) or ExtraCorporeal CO2 Removal (ECCO2R).

6. Pregnant or breastfeeding women, patients under guardianship or trusteeship, deprived of liberty

7. Patients who are moribund or for whom limitations of active therapies have been decided.

8. Any condition, which in the opinion of the investigator, would not allow the implementation of the study procedures.

Related Conditions & MeSH terms

• ARDS
• Pneumonia
• SARS-CoV 2 Pneumonia

Intervention

Other:
• blood sample and bronchoalveolar lavage
These patients are put on VM as part of their care and present a suspicion of a 1st episode of PAVM for which a microbiological sample is taken and a probabilistic antibiotic therapy is started with the PIP-TAZ association (D0). A plasma PIP-TAZ assay will be performed 48 hours after the start of antibiotic therapy with PIP-TAZ. Blood urea will be measured and a mini-LBA (performed with a Combicatheter®) will be performed to measure PIP-TAZ and urea in the ELF. On day 7 of the antibiotic therapy (last day of the planned antibiotic therapy), the same samples are taken and the same analyses are performed + bacteriology on the mini BAL. For patients for whom antibiotic therapy has been interrupted because of sterile samples, the samples taken at D7 will not be taken. The clinical outcome of the patient will then be recorded until D60.

Locations

Country	Name	City	State
France	Service Médecine Intensive Réanimation	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare the pulmonary diffusion of piperacillin	Dosage in the epithelial lining fluid	48 hours following antibiotics administration
Secondary	Pulmonary diffusion of tazobactam	Dosage in the epithelial lining fluid	48 hours following antibiotics administration
Secondary	Concentrations of piperacillin in effective pulmonary and plasma targets	Piperacillin concentrations in Epithelial Lining Fluid	48 hours following antibiotics administration
Secondary	Concentrations of piperacillin in effective pulmonary and plasma targets	Piperacillin concentrations in plasma	7 days following antibiotics administration
Secondary	Concentrations of tazobactam in effective pulmonary and plasma targets	Tazobactam concentrations in Epithelial Lining Fluid	7 days following antibiotics administration
Secondary	Concentrations of tazobactam in effective pulmonary and plasma targets	Tazobactam concentrations in Epitehlial Lining Fluid and plasma separately at H48 and 7 days after initiation of antibiotic therapy	48 hours following antibiotics administration