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Pulmonary Diffusion of Antibiotics in Patients Admitted for ARDS Following SARS-CoV-2 Pneumonia (ATB-COVID)

Primary Purpose

ARDS, SARS-CoV 2 Pneumonia

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

blood sample and bronchoalveolar lavage

About this trial

This is an interventional other trial for ARDS focused on measuring mechanical ventilation, antibiotics diffusion, ARDS, SARS-CoV 2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

Patients for whom PIP-TAZ is administered as a discontinuous infusion.
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
Patient with a second episode of PAVM.
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).
Patient on ExtraCorporeal Membrane Oxygenation (ECMO) or ExtraCorporeal CO2 Removal (ECCO2R).
Pregnant or breastfeeding women, patients under guardianship or trusteeship, deprived of liberty
Patients who are moribund or for whom limitations of active therapies have been decided.
Any condition, which in the opinion of the investigator, would not allow the implementation of the study procedures.

Sites / Locations

Service Médecine Intensive RéanimationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Patients positive to SARS-CoV 2

Patients negative to SARS-CoV 2

Arm Description

Patients admitted to the ICU and placed on VM following SARS-CoV-2 pneumonia

Patients admitted to the ICU and placed on VM outside of SARS-CoV-2 pneumonia

Outcomes

Primary Outcome Measures

Compare the pulmonary diffusion of piperacillin

Dosage in the epithelial lining fluid

Secondary Outcome Measures

Pulmonary diffusion of tazobactam

Dosage in the epithelial lining fluid

Concentrations of piperacillin in effective pulmonary and plasma targets

Piperacillin concentrations in Epithelial Lining Fluid

Concentrations of piperacillin in effective pulmonary and plasma targets

Piperacillin concentrations in plasma

Concentrations of tazobactam in effective pulmonary and plasma targets

Tazobactam concentrations in Epithelial Lining Fluid

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

Full Information

NCT ID

NCT05464680

First Posted

July 14, 2022

Last Updated

July 19, 2023

Sponsor

Assistance Publique Hopitaux De Marseille

1. Study Identification

Unique Protocol Identification Number

NCT05464680

Brief Title

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

Acronym

ATB-COVID

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 24, 2022 (Actual)

Primary Completion Date

November 23, 2024 (Anticipated)

Study Completion Date

February 23, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique Hopitaux De Marseille

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

ARDS, SARS-CoV 2 Pneumonia

Keywords

mechanical ventilation, antibiotics diffusion, ARDS, SARS-CoV 2

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Patients positive to SARS-CoV 2

Arm Type

Experimental

Arm Description

Patients admitted to the ICU and placed on VM following SARS-CoV-2 pneumonia

Arm Title

Patients negative to SARS-CoV 2

Arm Type

Sham Comparator

Arm Description

Patients admitted to the ICU and placed on VM outside of SARS-CoV-2 pneumonia

Intervention Type

Other

Intervention Name(s)

blood sample and bronchoalveolar lavage

Intervention Description

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.

Primary Outcome Measure Information:

Title

Compare the pulmonary diffusion of piperacillin

Description

Dosage in the epithelial lining fluid

Time Frame

48 hours following antibiotics administration

Secondary Outcome Measure Information:

Title

Pulmonary diffusion of tazobactam

Description

Dosage in the epithelial lining fluid

Time Frame

48 hours following antibiotics administration

Title

Concentrations of piperacillin in effective pulmonary and plasma targets

Description

Piperacillin concentrations in Epithelial Lining Fluid

Time Frame

48 hours following antibiotics administration

Title

Concentrations of piperacillin in effective pulmonary and plasma targets

Description

Piperacillin concentrations in plasma

Time Frame

7 days following antibiotics administration

Title

Concentrations of tazobactam in effective pulmonary and plasma targets

Description

Tazobactam concentrations in Epithelial Lining Fluid

Time Frame

7 days following antibiotics administration

Title

Concentrations of tazobactam in effective pulmonary and plasma targets

Description

Tazobactam concentrations in Epitehlial Lining Fluid and plasma separately at H48 and 7 days after initiation of antibiotic therapy

Time Frame

48 hours following antibiotics administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: Patients for whom PIP-TAZ is administered as a discontinuous infusion. 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 Patient with a second episode of PAVM. 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). Patient on ExtraCorporeal Membrane Oxygenation (ECMO) or ExtraCorporeal CO2 Removal (ECCO2R). Pregnant or breastfeeding women, patients under guardianship or trusteeship, deprived of liberty Patients who are moribund or for whom limitations of active therapies have been decided. Any condition, which in the opinion of the investigator, would not allow the implementation of the study procedures.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sami Hraiech

Phone

04 91 96 58 43

Ext

sami.hraiech@ap-hm.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

François Cremieux

Organizational Affiliation

AP-HM

Official's Role

Study Director

Facility Information:

Facility Name

Service Médecine Intensive Réanimation

City

Marseille

ZIP/Postal Code

13015

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sami Hraiech

sami.hraiech@ap-hm.fr

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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