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Completed

NCT Number: NCT05960006

A Study to Determine Pharmacokinetic Changes of Ceftriaxone in Patients With Liver Cirrhosis

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.

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Key information

Conditions

Antibiotic Toxicity Ascites Hepatic Bacterial Infections Bacterial Infections and Mycoses Ceftriaxone Overdose Digestive System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Fibrosis Infection, Bacterial Infections Kidney Diseases Liver Cirrhosis Liver Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Urogenital Diseases Urologic Diseases

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Amsterdam university medical centers location AMC

Amsterdam, 1105AZ, Netherlands

About this study

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

Who can participate

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

No intervention (observational study)

Other

There are no risks associated with participation because only waste material (blood and ascites) will be used for analysis and no additional blood collection or paracentesis will be performed in addition to standard-of-care. Moreover, hospital admittance and discharge, indication for interventional procedures, indication/initiation/duration/dosing of ceftriaxone, indication/timing/frequency of blood withdrawal for standard of care biochemical analysis and microbiological culturing as the indication, timing, frequency and duration of paracentesis are all decided by the treating physician independent of participation in the study. There are no extra site visits nor extra days of hospital admission. There is no direct benefit for participants of this explorative study. .

Primary outcomes

  1. Clearance (CL) of unbound ceftriaxone

    Time frame: 12 months

    Clearance (CL) of unbound ceftriaxone

  2. Volume of distribution (VD) of unbound ceftriaxone

    Time frame: 12 months

    Volume of distribution (VD) of unbound ceftriaxone

  3. Penetration rate of unbound ceftriaxone from blood to ascites

    Time frame: 12 months

    Penetration rate of unbound ceftriaxone from blood to ascites

  4. Elimination rate of unbound ceftriaxone from ascites by paracentesis

    Time frame: 12 months

    Elimination rate of unbound ceftriaxone from ascites by paracentesis

Secondary outcomes

  1. 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)

    Time frame: 12 months

    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)

  2. 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)

    Time frame: 12 months

    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)

  3. Explorative analysis on the effect of Child Pugh-score on individual pharmacokinetic parameters

    Time frame: 12 months

    Child Pugh score ranges from 5 points (minimum value) to 15 points (maximum value). Higher score means a worse outcome. Child Pugh score is a measure to determine the prognosis of patients with cirrhosis.

  4. Explorative analysis on the effect of MELD-score on individual pharmacokinetic parameters

    Time frame: 12 months

    MELD-score (Model for End-Stage Liver Disease, version: original, pre-2016) ranges from 6 points (minimum value) to 40 points (maximum value). Higher score means a worse outcome. MELD-score quantifies end-stage liver disease for transplant planning.

  5. Explorative analysis on the effect of CKD-stage on individual pharmacokinetic parameters

    Time frame: 12 months

    CKD (chronic kidney disease) stage ranges from stage 1 (minimum value) to stage 5 (maximum value). Higher score means a worse outcome. CKD-stage is based on the estimated glomerular filtration rate (eGFR, in mL/min/1.73m2) and refers to a measure of kidney function.

Sponsors and collaborators

Lead sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Other

Collaborators

  • Erasmus Medical Center

Registry information

Official study 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.

Acronym: TACTILE

Important dates

Study start
2023
Primary completion
2025
Study completion
2026
First posted
Jul 25, 2023
Registry last updated
Jan 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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