Extracorporeal Therapy and Therapeutic Drug Monitoring

Pharmacokinetics/Pharmacodynamics and Therapeutic Drug Monitoring of Novel β-lactams and β-lactamase Inhibitors in Critically Ill Patients Undergoing Extracorporeal Therapy

The aim of this study is to comparatively evaluate serum concentrations of continuously applied antibiotics in ICU patients, with and without ECMO/RRT support.

Study Overview

• Status: Not yet recruiting
• Conditions: ICU Patients With ECMO And-or RRT and With Gram Negative Infections Susceptible to BL-BLIs

Detailed Description

Among all patients being treated with new generation antibiotics (beta.lactams and beta-lactamase inhibitors), we will take into consideration the results of those admitted to intensive care units.

Effective antimicrobial treatment is critical to reduce their mortality associated with bacterial sepsis. They often also require extracorporeal supports, such as renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO), for their survival. However, few studies, limited only to some drugs, report the importance of therapeutic drug monitoring for adequate dose adjustment in these particular conditions of extracoporeal support.

The risk of reaching sub therapeutic or toxic levels is quite high, due to possible very significant variations in the pharmacokinetics of the drugs because of their interaction with the various components of the ECMO and RRT devices, the characteristics of the drug itself and the pathophysiological changes of the patients on ECMO and/or RRT.

Primary aim is to evaluate whether the standard prescriptions of beta lactams/beta lactamase inhibitors (BL/BLIs) are adequate to achieve the optimal PK/PD target also for ECMO and RRT (or combined) patients admitted to intensive care unit.

Secondary aims include to evaluate:

• the occurrence of sub-therapeutic and/or toxic drugs levels
• the proportion of patients with insufficient drugs levels in different subgroups (i.e., absence of extracorporeal therapy vs. ECMO; absence of extracorporeal therapy vs. RRT, absence of extracorporeal therapy vs ECMO and RRT) - the proportion of patients with toxic or sub-therapeutic drugs levels in the same subgroups;
• the proportion, when possible, of drugs level before and during the extracorporeal therapy, for the same patient;
• the occurrence of drug resistance by pathogens and their mechanism

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Simona De Gregori; Phone Number: +39 0382503647; Email: s.degregori@smatteo.pv.it

Study Locations

• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo
      • Contact: Simona De Gregori; Phone Number: +39 0382503647; Email: s.degregori@smatteo.pv.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

ICU patients with ECMO and/or RRT and with gram-negative infections susceptible to BL/BLIs

Description

Inclusion Criteria:

• adult patients (age 18y or older)
• admitted to ICU
• supported or not-supported with extracorporeal membrane oxygenation (ECMO) and/or renal replacement therapy (RRT)
• affected by gram-negative bacterial infections susceptible to the novel antibiotics.

Exclusion Criteria:

• Pediatric age (<18y)
• allergies to pharmaceutical and/or inactive drug ingredients (excipients)
• life expectancy less than 1 month
• body mass index (BMI) >45 kg/m2
• pregnancy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary aim	evaluate whether the standard prescriptions of beta lactams/beta lactamase inhibitors (BL/BLIs) are adequate to achieve the optimal PK/PD target also for ECMO and RRT (or combined) patients admitted to intensive care unit.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
occurrence of sub-therapeutic and/or toxic drugs levels	up to 24 months
proportion of patients with insufficient drugs levels in different subgroups	up to 24 months
proportion of patients with toxic or sub-therapeutic drugs levels in the same subgroups	up to 24 months
proportion, when possible, of drugs level before and during the extracorporeal therapy, for the same patient	up to 24 months
occurrence of drug resistance by pathogens and their mechanism	up to 24 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

Study Major Dates

• Study Start (Estimated): December 12, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: BL/BLIs in ICU - 2024

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No