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

Liver Cirrhosis Clinical Trial

— TACTILE  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05960006
• Other study ID #: W23_012 # 23.033
• Status: Recruiting
• Start date: July 10, 2023
• Est. completion date: September 10, 2024

Study information

• Verified date: July 2023
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Marten Alexander Lantinga, MD PhD
• Phone: +31 6500 91290
• Email: m.a.lantinga[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 10, 2024
• Est. primary completion date: July 10, 2024
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Antibiotic Toxicity
• Ascites
• Ascites Hepatic
• Bacterial Infections
• Fibrosis
• Infection, Bacterial
• Liver Cirrhosis
• Renal Insufficiency

Intervention

Other:
• No intervention
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. .

Locations

Country	Name	City	State
Netherlands	Amsterdam university medical centers location AMC	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clearance (CL) of unbound ceftriaxone	Clearance (CL) of unbound ceftriaxone	12 months
Primary	Volume of distribution (VD) of unbound ceftriaxone	Volume of distribution (VD) of unbound ceftriaxone	12 months
Primary	Penetration rate of unbound ceftriaxone from blood to ascites	Penetration rate of unbound ceftriaxone from blood to ascites	12 months
Primary	Elimination rate of unbound ceftriaxone from ascites by paracentesis	Elimination rate of unbound ceftriaxone from ascites by paracentesis	12 months
Secondary	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 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
Secondary	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)	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
Secondary	Explorative analysis on the effect of Child Pugh-score on individual pharmacokinetic parameters	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.	12 months
Secondary	Explorative analysis on the effect of MELD-score on individual pharmacokinetic parameters	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.	12 months
Secondary	Explorative analysis on the effect of CKD-stage on individual pharmacokinetic parameters	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.	12 months