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

NCT05960006 | Completed FDA Drug

• 1 other identifier: W23_012 # 23.033
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Cirrhosis; Renal Insufficiency; Ceftriaxone Overdose; Ascites Hepatic; Infection, Bacterial; Antibiotic Toxicity

Outcome Measures

Primary Outcomes (4)

• Clearance (CL) of unbound ceftriaxone

  Clearance (CL) of unbound ceftriaxone

  12 months

• Volume of distribution (VD) of unbound ceftriaxone

  Volume of distribution (VD) of unbound ceftriaxone

  12 months

• Penetration rate of unbound ceftriaxone from blood to ascites

  Penetration rate of unbound ceftriaxone from blood to ascites

  12 months

• Elimination rate of unbound ceftriaxone from ascites by paracentesis

  Elimination rate of unbound ceftriaxone from ascites by paracentesis

  12 months

Secondary Outcomes (5)

• 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)

  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)

  12 months

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

  12 months

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

  12 months

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

  12 months

Study Arms (1)

observational ceftriaxone

Patiënts with liver cirrhosis receiving ceftriaxone treatment.

Other: No intervention (observational study)

Interventions

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. .

observational ceftriaxone

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• None

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Erasmus Medical Center: collaborator

Study Sites (1)

Amsterdam university medical centers location AMC

Amsterdam, 1105AZ, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood and ascites

MeSH Terms

Conditions

Liver Cirrhosis; Renal Insufficiency; Bacterial Infections

Interventions

Observation

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Hepatology

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: July 25, 2023
• Study Start: July 10, 2023
• Primary Completion: April 10, 2025
• Study Completion: January 1, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

NL (1)