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

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ClinicalTrials.gov Identifier: NCT05960006
Recruitment Status : Recruiting
First Posted : July 25, 2023
Last Update Posted : July 25, 2023
Sponsor:
Collaborator:
Erasmus Medical Center
Information provided by (Responsible Party):
Marten A Lantinga, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Description
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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.

Condition or disease Intervention/treatment
Antibiotic Toxicity Liver Cirrhosis Renal Insufficiency Ceftriaxone Overdose Ascites Hepatic Infection, Bacterial Other: No intervention

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
Study Design
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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Case-Only
Time Perspective: Prospective
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.
Actual Study Start Date : July 10, 2023
Estimated Primary Completion Date : July 10, 2024
Estimated Study Completion Date : September 10, 2024

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
Ceftriaxone
Patiënts with liver cirrhosis receiving ceftriaxone treatment.
 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. .


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


Biospecimen Retention:   Samples With DNA
Blood and ascites

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05960006


Contacts
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Contact: Marten Alexander Lantinga, MD PhD +31 6500 91290 m.a.lantinga@amsterdamumc.nl

Locations
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Netherlands
Amsterdam university medical centers location AMC Recruiting
Amsterdam, Netherlands, 1105AZ
Contact: Marten Alexander Lantinga, MD PhD         
Principal Investigator: Reinier M van Hest, Pharm PhD         
Principal Investigator: Raoel Maan, MD PhD         
Principal Investigator: Midas B. Mulder, Pharm         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
More Information
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Responsible Party: Marten A Lantinga, MD PhD, Consultant Hepatology, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT05960006    
Other Study ID Numbers: W23_012 # 23.033
First Posted: July 25, 2023    Key Record Dates
Last Update Posted: July 25, 2023
Last Verified: July 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Individual participant data is available upon reasonable request.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Bacterial Infections
Liver Cirrhosis
Renal Insufficiency
Fibrosis
Ascites
Pathologic Processes
Liver Diseases
Digestive System Diseases
 Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Bacterial Infections and Mycoses
Infections