Acute Respiratory Distress SyndromeINF-ECMONCT05566665
Nosocomial Infections in ECMO Patients
An observational study of Acute Respiratory Distress Syndrome and Nosocomial Infection, run by Policlinico Hospital at 2 sites in Italy.
Trial summary
Nosocomial Infections (NI) are a common and dreadful complication for patients suffering from Acute Respiratory Distress Syndrome (ARDS) treated with Extracorporeal Membrane Oxygenation (ECMO). Unfortunately, no study has thoroughly evaluated NI in this fragile patient cohort. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Nosocomial Infection, Extracorporeal Membrane Oxygenation Complication
- What is being tested?
- Collection of blood and bronchoalveolar samples to study Pharmacokinetics of ceftazidime/avibactam, meropenem/varbobactam, ceftolozane/tazobactam, or cefiderocol
- How many people
- 200 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Jan 2023to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population for the Aim 1 study will comprise adult patients admitted to the aforementioned ICUs suffering from ARDS (as defined by the Berlin criteria) and treated with ECMO. The study population for the Aim 2 study will comprise the subgroup of patients as per Aim 1, whose clinical course is complicated by VAP necessitating antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol
Who may be able to join
- Age > 18 years
- Ongoing ECMO
- Adjunctive Inclusion Criterium for the sole Secondary Objective:
- Antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol.
Who cannot join
- ECPR
- ECMO as a bridge to Lung Transplantation
- Pregnancy
- Expected survival < 24 hours.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico
Milan, Milan, 20100
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Milan, MI, 20122
About this study
Official title: Nosocomial Infections in Patients Treated With Extracorporeal Membrane Oxygenation
Nosocomial Infections (NI) are a common and dreadful complication for patients suffering from Acute Respiratory Distress Syndrome (ARDS) treated with Extracorporeal Membrane Oxygenation (ECMO). Unfortunately, no study has thoroughly evaluated NI in this fragile patient cohort. Newly developed antibiotics may help manage such infections, but their pharmacokinetics (PK) during ECMO has not been evaluated.
Objectives of this prospective observational multicenter pharmacological no-profit study are: 1) describe incidence, microbial etiology, and resistance patterns, and assess risk factors for NIs in a large prospective cohort of ARDS patients undergoing ECMO. 2) provide a PK analysis of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefiderocol in adult patients undergoing ECMO Incidence, microbial etiology, and antibiotic resistance patterns of confirmed NIs will be prospectively collected and analyzed. In the subgroup of patients treated with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol as per clinical practice, blood and bronchoalveolar concentration of the antibiotic will be measured, and PK modeling carried out.
Read the detailed description
The most severe acute respiratory distress syndrome (ARDS) cases require extracorporeal membrane oxygenation (ECMO). ECMO is a life-support technique utilized in patients with reversible refractory respiratory failure. Nosocomial infections (NI) are common complications in ECMO patients due to predisposing factors such as patients' comorbidities, immunocompromise associated with the critical illness, and invasiveness of ECMO and other life support procedures. Few studies have assessed the incidence, risk factors, microbial etiology, and antibiotic resistance of NIs during ECMO. In a monocentric retrospective observational analysis, a high incidence of NI was detected in ECMO patients. The most common NI was ventilation-associated pneumonia (VAP), frequently caused by multidrug-resistant (MDR) bacteria. Patients developing an infection had a longer duration of ECMO and mechanical ventilation and a more prolonged ICU stay. The rate of MDR bacterial isolates was very high, and the first NI episode caused by MDR germs was an independent risk factor for death. To date, no prospective study has studied the epidemiology and clinical significance of NIs during ECMO. Better knowledge of NIs epidemiology during ECMO may allow us to target possibly causative agents using more specific empirical antibiotic therapy, increase accuracy, and optimize the timing of antimicrobial treatment. In turn, this may lead to better treatment of NIs in patients undergoing ECMO, thus reducing the overall burden of infections in such a fragile population and allowing a significant decrease in the costs of treatment.
Several new antimicrobial agents utilized for the treatment of MDR infections (i.e., ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, cefiderocol) have been granted approval in Europe for the treatment of VAP. Antibiotic efficacy in pneumonia requires sufficient unbound drug concentrations at the pulmonary site of infection, and determination of the bronchopulmonary availability of antibiotics in epithelial lining fluid (ELF) allows penetration into the lung to be characterized. While population pharmacokinetic (PK) models have been carried out in healthy volunteers, no data is available relative to the PK of those antibiotics ECMO patients. In general, ECMO has been shown to impact PK in three primary ways: direct extraction by the circuit increased volume of distribution, and altered clearance5. Thus, knowledge of the PK of these newly introduced antibiotic agents in ECMO patients suffering from VAP due to MDR bacteria may be of great clinical impact.
Based on these premises, in a large cohort of ECMO patients with ARDS, the investigators will carry out a prospective multicenter observational study to describe NIs and their risk factors. Overall, with this study, the investigators will significantly broaden the data as regards to NIs during ECMO.
In addition, in a subgroup of patients treated with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol for VAP during ECMO treatment, the investigators will carry out a pharmacokinetic study.
- Conditions
- Acute Respiratory Distress Syndrome, Nosocomial Infection, Extracorporeal Membrane Oxygenation Complication
- Being tested
- Collection of blood and bronchoalveolar samples to study Pharmacokinetics of ceftazidime/avibactam, meropenem/varbobactam, ceftolozane/tazobactam, or cefiderocol
- Medical subject headings
- Respiratory Distress Syndrome, Cross Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collection of blood and bronchoalveolar samples to study Pharmacokinetics of ceftazidime/avibactam, meropenem/varbobactam, ceftolozane/tazobactam, or cefiderocolDiagnostic test
The antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol will follow the standard clinical practice.
The concentration of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol will be measured at specific timepoints in plasma samples and bronchoalveolar lavage samples, and a PK analysis and modeling will be carried out .
| Study group | Role | What they receive |
|---|---|---|
| ECMO requiring patients | The study population for the Aim 1 study will comprise adult patients admitted to the participating ICUs treated with ECMO. The study population for the Aim 2 study will comprise the subgroup of patients as per Aim 1, whose clinical course is complicated by VAP necessitating antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol. | |
| Antibiotic treated ECMO requiring patients. | The study population for the Aim 2 study will comprise the subgroup of patients as per Aim 1, whose clinical course is complicated by VAP necessitating antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol. Receives: Diagnostic Test: Collection of blood and bronchoalveolar samples to study Pharmacokinetics of ceftazidime/avibactam, meropenem/varbobactam, ceftolozane/tazobactam, or cefiderocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of NIs in a large prospective cohort of patients undergoing ECMO.
Only microbiologically-confirmed infections will be considered. Accordingly, the composite outcome (i.e., infected patient) will be composed of the following NIs: ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI), bloodstream infection (BSI), and catheter-related bloodstream infection (CRBSI). Incidence of pulmonary aspergillosis and clostridium difficile colitis will be collected but not included in the composite outcome (i.e., infected patient). To carry out this aim, a supervisor for each participating center will be in charge of patients' follow-up. For each center, a critical care specialist and an infectious disease specialist will review the available clinical and laboratory data. Incidence will be expressed as: 1) percentage of patients who will develop a NI/total of patients; 2) rate of incidence: number of infection/total time at risk of NIs.
Measured: January 2023-December 2025
Microbial etiology of NIs in a large prospective cohort of patients undergoing ECMO.
Only microbiologically-confirmed infections will be considered. Accordingly, the composite outcome (i.e., infected patient) will be composed of the following NIs: ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI), bloodstream infection (BSI), and catheter-related bloodstream infection (CRBSI). Incidence of pulmonary aspergillosis and clostridium difficile colitis will be collected but not included in the composite outcome (i.e., infected patient). To carry out this aim, a supervisor for each participating center will be in charge of patients' follow-up. For each center, a critical care specialist and an infectious disease specialist will review the available clinical and laboratory data. Different microbial etiology will be described according to simple descriptive statistics methods.
Measured: January 2023-December 2025
Resistance patterns of NIs in a large prospective cohort of patients undergoing ECMO.
Only microbiologically-confirmed infections will be considered. Accordingly, the composite outcome (i.e., infected patient) will be composed of the following NIs: ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI), bloodstream infection (BSI), and catheter-related bloodstream infection (CRBSI). Incidence of pulmonary aspergillosis and clostridium difficile colitis will be collected but not included in the composite outcome (i.e., infected patient). To carry out this aim, a supervisor for each participating center will be in charge of patients' follow-up. For each center, a critical care specialist and an infectious disease specialist will review the available clinical and laboratory data. Resistance patterns of NIs' microbes will be described according to simple descriptive statistics methods.
Measured: January 2023-December 2025
Risk factors of NIs in a large prospective cohort of patients undergoing ECMO.
Only microbiologically-confirmed infections will be considered. Accordingly, the composite outcome (i.e., infected patient) will be composed of the following NIs: ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI), bloodstream infection (BSI), and catheter-related bloodstream infection (CRBSI). Incidence of pulmonary aspergillosis and clostridium difficile colitis will be collected but not included in the composite outcome (i.e., infected patient). To carry out this aim, a supervisor for each participating center will be in charge of patients' follow-up. For each center, a critical care specialist and an infectious disease specialist will review the available clinical and laboratory data. Multivariate analysis will be conducted to evaluate risk factors of NIs. For each risk factor identified Odds Ratio with 95% Confidence Interval will be reported.
Measured: January 2023-December 2025
Secondary outcomes (2)
Plasma concentration of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefiderocol in adult patients undergoing ECMO
For this aim, there will be no modification of patients' treatment and antibiotic use. The antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol will follow the standard clinical practice.
The concentration of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol will be measured in plasma samples at four specific timepoints (the first before the 5th administration of antibiotic, and then 1, 2 and 4 hours after the administration) to evaluate Maximum Plasmatic Concentration of antibiotic and its pharmacokinetics.
Measured: January 2023-December 2025
Bronchoalveolar lavage concentration of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefiderocol in adult patients undergoing ECMO
For this aim, there will be no modification of patients' treatment and antibiotic use. The antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol will follow the standard clinical practice.
The concentration of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol will be measured in bronchoalveolar lavage (BAL) samples before the 5th administration of antibiotic to evaluate BAL Concentration of antibiotic.
Measured: January 2023-December 2024
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2022
- Study start1 Jan 2023
- Primary completion31 Mar 2026
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Policlinico Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Giacomo Grasselli, Policlinico Hospital
- Investigators
- Vittorio Scaravilli, MD, Principal investigator, University of MilanGiacomo Grasselli, MD, Principal investigator, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05566665
- Sponsor's protocol ID
- INF-ECMO
- Acronym
- INF-ECMO
- Status last verified
- Jun 2026
- First submitted
- 13 Sep 2022
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
PubMed 26903337Schmidt M, Hajage D, Lebreton G, Monsel A, Voiriot G, Levy D, Baron E, Beurton A, Chommeloux J, Meng P, Nemlaghi S, Bay P, Leprince P, Demoule A, Guidet B, Constantin JM, Fartoukh M, Dres M, Combes A; Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE) Sorbonne Universite; Paris-Sorbonne ECMO-COVID investigators. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study. Lancet Respir Med. 2020 Nov;8(11):1121-1131. doi: 10.1016/S2213-2600(20)30328-3. Epub 2020 Aug 13.
PubMed 32798468Grasselli G, Scaravilli V, Di Bella S, Biffi S, Bombino M, Patroniti N, Bisi L, Peri AM, Pesenti A, Gori A, Alagna L. Nosocomial Infections During Extracorporeal Membrane Oxygenation: Incidence, Etiology, and Impact on Patients' Outcome. Crit Care Med. 2017 Oct;45(10):1726-1733. doi: 10.1097/CCM.0000000000002652.
PubMed 28777198Yusuf E, Bax HI, Verkaik NJ, van Westreenen M. An Update on Eight "New" Antibiotics against Multidrug-Resistant Gram-Negative Bacteria. J Clin Med. 2021 Mar 4;10(5):1068. doi: 10.3390/jcm10051068.
PubMed 33806604Sherwin J, Heath T, Watt K. Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature. Clin Ther. 2016 Sep;38(9):1976-94. doi: 10.1016/j.clinthera.2016.07.169. Epub 2016 Aug 21.
PubMed 27553752ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
PubMed 22797452Falcone M, Menichetti F, Cattaneo D, Tiseo G, Baldelli S, Galfo V, Leonildi A, Tagliaferri E, Di Paolo A, Pai MP. Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients. J Antimicrob Chemother. 2021 Mar 12;76(4):1025-1031. doi: 10.1093/jac/dkaa549.
PubMed 33378458Castagnola E, Cangemi G, Mesini A, Castellani C, Martelli A, Cattaneo D, Mattioli F. Pharmacokinetics and pharmacodynamics of antibiotics in cystic fibrosis: a narrative review. Int J Antimicrob Agents. 2021 Sep;58(3):106381. doi: 10.1016/j.ijantimicag.2021.106381. Epub 2021 Jun 19.
PubMed 34157401Grasselli G, Scaravilli V, Mangioni D, Scudeller L, Alagna L, Bartoletti M, Bellani G, Biagioni E, Bonfanti P, Bottino N, Coloretti I, Cutuli SL, De Pascale G, Ferlicca D, Fior G, Forastieri A, Franzetti M, Greco M, Guzzardella A, Linguadoca S, Meschiari M, Messina A, Monti G, Morelli P, Muscatello A, Redaelli S, Stefanini F, Tonetti T, Antonelli M, Cecconi M, Foti G, Fumagalli R, Girardis M, Ranieri M, Viale P, Raviglione M, Pesenti A, Gori A, Bandera A. Hospital-Acquired Infections in Critically Ill Patients With COVID-19. Chest. 2021 Aug;160(2):454-465. doi: 10.1016/j.chest.2021.04.002. Epub 2021 Apr 20.
PubMed 33857475
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nosocomial Infections in Patients Treated With Extracorporeal Membrane Oxygenation
- ClinicalTrials.gov ID
- NCT05566665
- Acronym / sponsor ID
- INF-ECMO / INF-ECMO
- Conditions
- Acute Respiratory Distress Syndrome, Nosocomial Infection, Extracorporeal Membrane Oxygenation Complication
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Policlinico HospitalUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 31 Mar 2026 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 4 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Nosocomial Infections (NI) are a common and dreadful complication for patients suffering from Acute Respiratory Distress Syndrome (ARDS) treated with Extracorporeal Membrane Oxygenation (ECMO). Unfortunately, no study has thoroughly evaluated NI in this fragile patient cohort. Newly developed antibiotics may help manage such infections, but their pharmacokinetics (PK) during ECMO has not been evaluated.
Objectives of this prospective observational multicenter pharmacological no-profit study are: 1) describe incidence, microbial etiology, and resistance patterns, and assess risk factors for NIs in a large prospective cohort of ARDS patients undergoing ECMO. 2) provide a PK analysis of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefiderocol in adult patients undergoing ECMO Incidence, microbial etiology, and antibiotic resistance patterns of confirmed NIs will be prospectively collected and analyzed. In the subgroup of patients treated with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol as per clinical practice, blood and bronchoalveolar concentration of the antibiotic will be measured, and PK modeling carried out.
Detailed description
The most severe acute respiratory distress syndrome (ARDS) cases require extracorporeal membrane oxygenation (ECMO). ECMO is a life-support technique utilized in patients with reversible refractory respiratory failure. Nosocomial infections (NI) are common complications in ECMO patients due to predisposing factors such as patients' comorbidities, immunocompromise associated with the critical illness, and invasiveness of ECMO and other life support procedures. Few studies have assessed the incidence, risk factors, microbial etiology, and antibiotic resistance of NIs during ECMO. In a monocentric retrospective observational analysis, a high incidence of NI was detected in ECMO patients. The most common NI was ventilation-associated pneumonia (VAP), frequently caused by multidrug-resistant (MDR) bacteria. Patients developing an infection had a longer duration of ECMO and mechanical ventilation and a more prolonged ICU stay. The rate of MDR bacterial isolates was very high, and the first NI episode caused by MDR germs was an independent risk factor for death. To date, no prospective study has studied the epidemiology and clinical significance of NIs during ECMO. Better knowledge of NIs epidemiology during ECMO may allow us to target possibly causative agents using more specific empirical antibiotic therapy, increase accuracy, and optimize the timing of antimicrobial treatment. In turn, this may lead to better treatment of NIs in patients undergoing ECMO, thus reducing the overall burden of infections in such a fragile population and allowing a significant decrease in the costs of treatment.
Several new antimicrobial agents utilized for the treatment of MDR infections (i.e., ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, cefiderocol) have been granted approval in Europe for the treatment of VAP. Antibiotic efficacy in pneumonia requires sufficient unbound drug concentrations at the pulmonary site of infection, and determination of the bronchopulmonary availability of antibiotics in epithelial lining fluid (ELF) allows penetration into the lung to be characterized. While population pharmacokinetic (PK) models have been carried out in healthy volunteers, no data is available relative to the PK of those antibiotics ECMO patients. In general, ECMO has been shown to impact PK in three primary ways: direct extraction by the circuit increased volume of distribution, and altered clearance5. Thus, knowledge of the PK of these newly introduced antibiotic agents in ECMO patients suffering from VAP due to MDR bacteria may be of great clinical impact.
Based on these premises, in a large cohort of ECMO patients with ARDS, the investigators will carry out a prospective multicenter observational study to describe NIs and their risk factors. Overall, with this study, the investigators will significantly broaden the data as regards to NIs during ECMO.
In addition, in a subgroup of patients treated with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol for VAP during ECMO treatment, the investigators will carry out a pharmacokinetic study.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ECMO requiring patients | – | –The study population for the Aim 1 study will comprise adult patients admitted to the participating ICUs treated with ECMO. The study population for the Aim 2 study will comprise the subgroup of patients as per Aim 1, whose clinical course is complicated by VAP necessitating antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol. |
| Antibiotic treated ECMO requiring patients. | – | Diagnostic Test: Collection of blood and bronchoalveolar samples to study Pharmacokinetics of ceftazidime/avibactam, meropenem/varbobactam, ceftolozane/tazobactam, or cefiderocolThe study population for the Aim 2 study will comprise the subgroup of patients as per Aim 1, whose clinical course is complicated by VAP necessitating antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population for the Aim 1 study will comprise adult patients admitted to the aforementioned ICUs suffering from ARDS (as defined by the Berlin criteria) and treated with ECMO. The study population for the Aim 2 study will comprise the subgroup of patients as per Aim 1, whose clinical course is complicated by VAP necessitating antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol
Key inclusion criteria (4 listed)
- Age > 18 years
- Ongoing ECMO
- Antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol.
Key exclusion criteria (4 listed)
- ECPR
- ECMO as a bridge to Lung Transplantation
- Pregnancy
- Expected survival < 24 hours.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Collection of blood and bronchoalveolar samples to study Pharmacokinetics of ceftazidime/avibactam, meropenem/varbobactam, ceftolozane/tazobactam, or cefiderocolThe antibiotic treatment with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol will follow the standard clinical practice. The concentration of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol will be measured at specific timepoints in plasma samples and bronchoalveolar lavage samples, and a PK analysis and modeling will be carried out . | Diagnostic test | Antibiotic treated ECMO requiring patients. |
Primary outcome
Incidence of NIs in a large prospective cohort of patients undergoing ECMO.
Time frame: January 2023-December 2025
Only microbiologically-confirmed infections will be considered. Accordingly, the composite outcome (i.e., infected patient) will be composed of the following NIs: ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI), bloodstream infection (BSI), and catheter-related bloodstream infection (CRBSI). Incidence of pulmonary aspergillosis and clostridium difficile colitis will be collected but not included in the composite outcome (i.e., infected patient). To carry out this aim, a supervisor for each participating center will be in charge of patients' follow-up. For each center, a critical care specialist and an infectious disease specialist will review the available clinical and laboratory data. Incidence will be expressed as: 1) percentage of patients who will develop a NI/total of patients; 2) rate of incidence: number of infection/total time at risk of NIs.
Microbial etiology of NIs in a large prospective cohort of patients undergoing ECMO.
Time frame: January 2023-December 2025
Only microbiologically-confirmed infections will be considered. Accordingly, the composite outcome (i.e., infected patient) will be composed of the following NIs: ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI), bloodstream infection (BSI), and catheter-related bloodstream infection (CRBSI). Incidence of pulmonary aspergillosis and clostridium difficile colitis will be collected but not included in the composite outcome (i.e., infected patient). To carry out this aim, a supervisor for each participating center will be in charge of patients' follow-up. For each center, a critical care specialist and an infectious disease specialist will review the available clinical and laboratory data. Different microbial etiology will be described according to simple descriptive statistics methods.
Resistance patterns of NIs in a large prospective cohort of patients undergoing ECMO.
Time frame: January 2023-December 2025
Only microbiologically-confirmed infections will be considered. Accordingly, the composite outcome (i.e., infected patient) will be composed of the following NIs: ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI), bloodstream infection (BSI), and catheter-related bloodstream infection (CRBSI). Incidence of pulmonary aspergillosis and clostridium difficile colitis will be collected but not included in the composite outcome (i.e., infected patient). To carry out this aim, a supervisor for each participating center will be in charge of patients' follow-up. For each center, a critical care specialist and an infectious disease specialist will review the available clinical and laboratory data. Resistance patterns of NIs' microbes will be described according to simple descriptive statistics methods.
Risk factors of NIs in a large prospective cohort of patients undergoing ECMO.
Time frame: January 2023-December 2025
Only microbiologically-confirmed infections will be considered. Accordingly, the composite outcome (i.e., infected patient) will be composed of the following NIs: ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI), bloodstream infection (BSI), and catheter-related bloodstream infection (CRBSI). Incidence of pulmonary aspergillosis and clostridium difficile colitis will be collected but not included in the composite outcome (i.e., infected patient). To carry out this aim, a supervisor for each participating center will be in charge of patients' follow-up. For each center, a critical care specialist and an infectious disease specialist will review the available clinical and laboratory data. Multivariate analysis will be conducted to evaluate risk factors of NIs. For each risk factor identified Odds Ratio with 95% Confidence Interval will be reported.
2 secondary outcomes
Plasma concentration of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefiderocol in adult patients undergoing ECMO
Time frame: January 2023-December 2025
Bronchoalveolar lavage concentration of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefiderocol in adult patients undergoing ECMO
Time frame: January 2023-December 2024
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
- Background: PubMed 26903337Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
- Background: PubMed 32798468Schmidt M, Hajage D, Lebreton G, Monsel A, Voiriot G, Levy D, Baron E, Beurton A, Chommeloux J, Meng P, Nemlaghi S, Bay P, Leprince P, Demoule A, Guidet B, Constantin JM, Fartoukh M, Dres M, Combes A; Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE) Sorbonne Universite; Paris-Sorbonne ECMO-COVID investigators. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study. Lancet Respir Med. 2020 Nov;8(11):1121-1131. doi: 10.1016/S2213-2600(20)30328-3. Epub 2020 Aug 13.
- Background: PubMed 28777198Grasselli G, Scaravilli V, Di Bella S, Biffi S, Bombino M, Patroniti N, Bisi L, Peri AM, Pesenti A, Gori A, Alagna L. Nosocomial Infections During Extracorporeal Membrane Oxygenation: Incidence, Etiology, and Impact on Patients' Outcome. Crit Care Med. 2017 Oct;45(10):1726-1733. doi: 10.1097/CCM.0000000000002652.
- Background: PubMed 33806604Yusuf E, Bax HI, Verkaik NJ, van Westreenen M. An Update on Eight "New" Antibiotics against Multidrug-Resistant Gram-Negative Bacteria. J Clin Med. 2021 Mar 4;10(5):1068. doi: 10.3390/jcm10051068.
- Background: PubMed 27553752Sherwin J, Heath T, Watt K. Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature. Clin Ther. 2016 Sep;38(9):1976-94. doi: 10.1016/j.clinthera.2016.07.169. Epub 2016 Aug 21.
- Background: PubMed 22797452ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
- Background: PubMed 33378458Falcone M, Menichetti F, Cattaneo D, Tiseo G, Baldelli S, Galfo V, Leonildi A, Tagliaferri E, Di Paolo A, Pai MP. Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients. J Antimicrob Chemother. 2021 Mar 12;76(4):1025-1031. doi: 10.1093/jac/dkaa549.
- Background: PubMed 34157401Castagnola E, Cangemi G, Mesini A, Castellani C, Martelli A, Cattaneo D, Mattioli F. Pharmacokinetics and pharmacodynamics of antibiotics in cystic fibrosis: a narrative review. Int J Antimicrob Agents. 2021 Sep;58(3):106381. doi: 10.1016/j.ijantimicag.2021.106381. Epub 2021 Jun 19.
- Background: PubMed 33857475Grasselli G, Scaravilli V, Mangioni D, Scudeller L, Alagna L, Bartoletti M, Bellani G, Biagioni E, Bonfanti P, Bottino N, Coloretti I, Cutuli SL, De Pascale G, Ferlicca D, Fior G, Forastieri A, Franzetti M, Greco M, Guzzardella A, Linguadoca S, Meschiari M, Messina A, Monti G, Morelli P, Muscatello A, Redaelli S, Stefanini F, Tonetti T, Antonelli M, Cecconi M, Foti G, Fumagalli R, Girardis M, Ranieri M, Viale P, Raviglione M, Pesenti A, Gori A, Bandera A. Hospital-Acquired Infections in Critically Ill Patients With COVID-19. Chest. 2021 Aug;160(2):454-465. doi: 10.1016/j.chest.2021.04.002. Epub 2021 Apr 20.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vittorio Scaravilli, MD principal investigator
University of Milan
Giacomo Grasselli, MD principal investigator
University of Milan
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Respiratory Distress Syndrome and Nosocomial Infection, run by Policlinico Hospital at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of NIs in a large prospective cohort of patients undergoing ECMO. (time frame: January 2023-December 2025). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05566665, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.