Amoxicillin; Clavulanic acid for Ventilator-associated pneumonia | Intensive care

Inclusion criteria

• {"criterion_text":"- Adult patient is ≥18"}
• {"criterion_text":"- Diagnosis of microbiologically confirmed of first episode of VAP"}
• {"criterion_text":"- - Initial appropriate antibiotic therapy (whether empirical or not)"}
• {"criterion_text":"- Written informed consent from the patient or a legal representative if appropriate. If absence of a legal representative the patient may be included in emergency procedure"}
• {"criterion_text":"- Definitive diagnosis of VAP (in agreement with international guidelines) is defined by association: -\tPatient under MV>48 hours at the time of the microbiological sampling -\tNew pulmonary infiltrate of which an infectious origin is strongly suspected -\tworsening oxygenation -\tHave the following clinical criteria within the 24 hours prior to the first dose of antibiotic therapy \tPurulent tracheal secretions \tAnd at least 1 of the following : •\tDocumented fever (body temperature >38,3°C) •\tHypothermia (body temperature <35°C) •\tWhite blood cell (WBC) count >10,000 cells/mm3 or <4,000 cells/mm3 -\tmicrobiological criteria (positive quantitative culture of a lower respiratory tract (LRT): bronchoalveolar lavage fluid (BAL) (significant threshold ≥104 colony-forming units/mL) or plugged telescopic catheter (PTC) (significant threshold ≥ 103 colony-forming units/mL) or quantitative endotracheal aspirate (ETA) distal pulmonary secretion samples (significant threshold ≥105 colony-forming units/mL)"}

Exclusion criteria

• {"criterion_text":"-\tPatient under selective decontamination of the digestive tract"}
• {"criterion_text":"-\tDuration of antibiotic therapy prior to inclusion > 72h (for any reason) appropriate to the germs found in the bacterial documentation of the first episode of VAP"}
• {"criterion_text":"-\tInclusion in another interventional study concerning empirical antimicrobial strategies"}
• {"criterion_text":"-\tMoribund (IGS II>80)"}
• {"criterion_text":"-\tThoracic trauma with Abbreviated Injury Scale (AIS) thorax  3"}
• {"criterion_text":"-\tSeverely immunocompromised patients (such as congenital immunodeficiency, neutropenia (<1leucocyte/ml or <0.5 neutrophil/ml) or acute hematologic malignancy or stem cell transplant, HIV infection with CD4 count below 200/mm3)"}
• {"criterion_text":"-\tPatients undergoing immunosuppressive therapy or long term corticotherapy > 0.5 mg/kg"}
• {"criterion_text":"-\tVAP due to: Pseudomonas aeruginosa, Carbapenem-resistant Acinetobacter spp, Carbapenem-resistant EnterobacteriaceaeBacterial VAP occurring in the context of co-infection of COVID-19 or other viral pneumonia (confirmed by RT-PCR)"}
• {"criterion_text":"-\tPatients with empyema, necrotizing and abscessed pneumonia"}
• {"criterion_text":"-\tPatients requiring extracorporeal oxygen therapy (ECMO), either veno-venous or veno-arterial"}
• {"criterion_text":"- Pregnant women"}
• {"criterion_text":"-\tNo health insurance coverage"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is a composite endpoint with non-inferiority criteria including: 1. all-cause mortality (ACM) measured at day 28 after initiation of antibiotic therapy OR 2. Treatment failure defined by signs of pneumonia within 72 hours after the end antibiotic therapy at the test of cure visit OR 3. New episode of microbiologically confirmed VAP from 72 hours after the end antibiotic treatment to day 28 after initiation of VAP antibiotic treatment","definition_or_measurement_approach":"Composite hierarchical non-inferiority endpoint: 1) All-cause mortality measured at day 28 after initiation of antibiotic therapy; OR 2) Treatment failure defined by signs of pneumonia within 72 hours after the end of antibiotic therapy at the test-of-cure visit; OR 3) New episode of microbiologically confirmed VAP occurring from 72 hours after the end of antibiotic treatment up to day 28 after initiation of VAP antibiotic treatment."}

Secondary endpoints

• {"endpoint_text":"- 1)\tRate of all-cause mortality","definition_or_measurement_approach":""}
• {"endpoint_text":"- 2)\tRate of treatment failure","definition_or_measurement_approach":""}
• {"endpoint_text":"- 3)\tRate of new episode of VAP","definition_or_measurement_approach":""}
• {"endpoint_text":"- 4)\tNumber of antibiotic free alive-days from initiation of VAP antibiotic therapy to day 28","definition_or_measurement_approach":"Count of antibiotic-free alive days from initiation of VAP antibiotic therapy until day 28."}
• {"endpoint_text":"- 5)\tGlobal score constructed with the DOOR and RADAR. Overall clinical outcome at day 28, from most to least desirable are: 1. Survival, clinical cure 2. Survival, new pulmonary infection 3. Death","definition_or_measurement_approach":"Composite global score using DOOR and RADAR to rank overall clinical outcome at day 28 (ordered as survival with clinical cure > survival with new pulmonary infection > death)."}
• {"endpoint_text":"- 6)\tDuration of invasive MV, at day 28 after inclusion, defined as total of days under MV","definition_or_measurement_approach":"Total number of days on invasive mechanical ventilation measured up to day 28 after inclusion."}
• {"endpoint_text":"- 7)\tLength of ICU stay at day 28 after inclusion, defined by the number of days between inclusion and ICU discharge or in-ICU death.","definition_or_measurement_approach":"Number of days between inclusion and ICU discharge or in-ICU death, assessed at day 28."}
• {"endpoint_text":"- 8)\tRate of VAP recurrence by the intensivist at day 28","definition_or_measurement_approach":"Clinician-assessed recurrence of VAP by intensivist at day 28."}
• {"endpoint_text":"- 9)\tRate of antibiotic related side effects","definition_or_measurement_approach":"Rate of antibiotic-associated adverse events (e.g., gastrointestinal symptoms, Clostridium difficile colitis, acute kidney injury, skin reactions) assessed by day 28."}
• {"endpoint_text":"- 10)\tRate of acquisition of MDR bacteria at day 28 defined as the identification of a MDR bacteria carriage not present at admission","definition_or_measurement_approach":"Identification of new carriage of multidrug-resistant (MDR) bacteria at day 28 that was not present at admission."}
• {"endpoint_text":"- 11)\tRate of death at days 28 and 90 at day 28","definition_or_measurement_approach":"Mortality rates assessed at day 28 and at day 90."}
• {"endpoint_text":"- 12)\tRate of non-interruption of antibiotic therapy despite a positive clinical cure in the intervention group only at day 28 after inclusion.","definition_or_measurement_approach":"Proportion in the intervention group who did not have antibiotics stopped despite meeting clinical cure criteria, assessed at day 28."}
• {"endpoint_text":"- 13)\tTotal cumulative costs of antibiotics at day 28 and incremental cost effectiveness ratio","definition_or_measurement_approach":"Total cumulative antibiotic costs at day 28 and calculation of incremental cost-effectiveness ratio."}

France

Earliest CTIS Part Ii Submission Date

30-08-2024

Latest Decision Or Authorization Date

24-02-2026

Processing Time Days

543

Number Of Sites

29

Number Of Participants

590

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France