Clinical trial NCT05960006: A Study to Determine Pharmacokinetic Changes of Ceftriaxone in Patients With Liver Cirrhosis
Official title: An Observational Explorative Study to Determine Pharmacokinetic Changes of Ceftriaxone in Blood and Ascites in Patients Admitted With Decompensated Liver Cirrhosis With or Without Renal Impairment.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Antibiotic Toxicity
Liver Cirrhosis
Renal Insufficiency
Ceftriaxone Overdose
Ascites Hepatic
Infection, Bacterial
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
First posted: 2023-07-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All admitted patients with the diagnosis of liver cirrhosis and ascites who receive at least a single dose of ceftriaxone during the current admission and receive diagnostic and/or therapeutic paracentesis following administration of ceftriaxone are suitable for inclusion in this study. The indication for diagnostic and/or therapeutic paracentesis is made upon the discretion of the treating physician following standard-of-care protocols.

Brief summary: The investigators designed an observational multicenter explorative in vivo study to investigate the changes in ceftriaxone pharmacokinetics in blood and ascites. The investigators will include a total of 20 patients with liver cirrhosis admitted to the ward of participating hospitals. Patients are eligible when receiving ceftriaxone and concomitantly receive paracentesis. The investigators will collect all available waste blood samples of each participant, starting from study entry up until 48 hours after the last dosing interval of ceftriaxone. The investigators will collect all available waste ascites samples of each participant up until 48 hours after the last dosing interval of ceftriaxone. Duration of the trial: The study duration is variable and depends on the duration of ceftriaxone treatment and duration of hospital admission, which both are determined by the treating physician and is not influenced by study participation. Patients will be eligible for study inclusion when patients received (a single dose of) ceftriaxone treatment and undergo paracentesis during ceftriaxone treatment. The study will end 48 hours after the last dosing interval of ceftriaxone or until hospital discharge, whichever comes first. Study timeline: The investigators expect to enrol 1-2 participants every month. The total enrolment time will thus be approximately 12 months.

Detailed description: Objective: The primary objective is to determine the changes in ceftriaxone pharmacokinetics in blood and ascites in patients with decompensated liver cirrhosis to guide ceftriaxone dosing in these patients.

Study design: Observational explorative multicentre study

Study population: Adults (\>18 years) with decompensated liver cirrhosis with the presence of ascites admitted to the clinical ward of participating centres who receive ceftriaxone and concomitantly undergo paracentesis during active antibiotic treatment.

Intervention: No intervention, the investigators will only collect the available waste blood and ascites samples.

Main study parameters/endpoints:

* Clearance (CL) of unbound ceftriaxone
* Volume of distribution (VD) of unbound ceftriaxone
* Penetration rate of unbound ceftriaxone from blood to ascites
* Elimination rate of unbound ceftriaxone from ascites by paracentesis

Secondary study parameters are:

* Target attainment of ceftriaxone in blood, defined as the unbound plasma concentration of ceftriaxone above at least one time the minimal inhibitory concentration (MIC) for 50% of the dosing interval (50%fT \> 1MIC).
* Target attainment of ceftriaxone in ascites, defined as the unbound ascites concentration of ceftriaxone above at least one time the minimal inhibitory concentration (MIC) for 50% of the dosing interval (50%fT \> 1MIC).
* Explorative analysis on the effects of liver disease severity (Child Pugh, MELD-score) and renal insufficiency (CKD-stage) on individual pharmacokinetic parameters

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years
* Clinical, radiological and/or histological diagnosis of liver cirrhosis and portal hypertension
* Presence of ascites
* Receiving ceftriaxone in the context of prophylaxis or treatment of infection
* Indication for diagnostic and/or therapeutic paracentesis
* Providing oral informed consent

Exclusion Criteria:

* None

Primary outcomes:
measure: Clearance (CL) of unbound ceftriaxone
timeFrame: 12 months
measure: Volume of distribution (VD) of unbound ceftriaxone
timeFrame: 12 months
measure: Penetration rate of unbound ceftriaxone from blood to ascites
timeFrame: 12 months
measure: Elimination rate of unbound ceftriaxone from ascites by paracentesis
timeFrame: 12 months
Secondary outcomes:
measure: Target attainment of ceftriaxone in blood, defined as the unbound plasma concentration of ceftriaxone above at least one time the minimal inhibitory concentration (MIC) for 50% of the dosing interval (50%fT > 1MIC)
timeFrame: 12 months
measure: Target attainment of ceftriaxone in ascites, defined as the unbound ascites concentration of ceftriaxone above at least one time the minimal inhibitory concentration (MIC) for 50% of the dosing interval (50%fT > 1MIC)
timeFrame: 12 months
measure: Explorative analysis on the effect of Child Pugh-score on individual pharmacokinetic parameters
timeFrame: 12 months
measure: Explorative analysis on the effect of MELD-score on individual pharmacokinetic parameters
timeFrame: 12 months
measure: Explorative analysis on the effect of CKD-stage on individual pharmacokinetic parameters
timeFrame: 12 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam university medical centers location AMC
Study officials:
References: