Antibiotic Dosing in Patients on Intermittent Hemodialysis

NCT03909698 | Completed

• 1 other identifier: UGent_ABdosing
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The adequacy of the currently used dosing regimen of glycopeptides (vancomycin and teicoplanin) and beta-lactam antibiotics (amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidim) in patients with end-stage kidney disease receiving intermittent hemodialysis is studied by evaluating pharmacokinetics-pharmacodynamics (PK-PD) target attainment. A population pharmacokinetic study is performed to assist the selection of the optimal individualized dose for patients undergoing intermittent dialysis, taking into consideration as many relevant variables as possible.

Conditions

Kidney Failure, Chronic; Antibiotics; Hemodialysis

Outcome Measures

Primary Outcomes (10)

• Blood concentrations with maximal antimicrobial activity versus current dosing regimens for vancomycin

  Measured free and total concentration of the glycopeptide vancomycin is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: Area Under the Curve (AUC) from 0-24h in steady-state divided by the Minimum Inhibitory Concentration (MIC) of the suspected pathogen should be \>=400 for vancomycin.

  9/2016 - 12/2021

• Blood concentrations with maximal antimicrobial activity versus current dosing regimens for teicoplanin

  Measured free and total concentration of the glycopeptide teicoplanin is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: Area Under the Curve (AUC) from 0-24h in steady-state divided by the Minimum Inhibitory Concentration (MIC) of the suspected pathogen should be \>=750 for teicoplanin.

  9/2016 - 12/2021

• Blood concentrations with maximal antimicrobial activity versus current dosing regimens for amoxicillin-clavulanic acid

  Measured concentration of the beta-lactam amoxicillin-clavulanic acid is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%.

  9/2016 - 12/2021

• Blood concentrations with maximal antimicrobial activity versus current dosing regimens for piperacillin-tazobactam

  Measured concentration of the beta-lactam piperacillin-tazobactam is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%.

  9/2016 - 12/2021

• Blood concentrations with maximal antimicrobial activity versus current dosing regimens for ceftazidim

  Measured concentration of the beta-lactam ceftazidim is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%.

  9/2016 - 12/2021

• Pharmacokinetics of vancomycin in patients undergoing intermittent hemodialysis

  Population pharmacokinetic modeling is performed based on the measured vancomycin concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured vancomycin concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.

  9/2016 - 12/2021

• Pharmacokinetics of teicoplanin in patients undergoing intermittent hemodialysis

  Population pharmacokinetic modeling is performed based on the measured teicoplanin concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured teicoplanin concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.

  9/2016 - 12/2021

• Pharmacokinetics of amoxicillin-clavulanic acid in patients undergoing intermittent hemodialysis

  Population pharmacokinetic modeling is performed based on the measured amoxicillin-clavulanic acid concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured amoxicillin-clavulanic acid concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.

  9/2016 - 12/2021

• Pharmacokinetics of piperacillin-tazobactam in patients undergoing intermittent hemodialysis

  Population pharmacokinetic modeling is performed based on the measured piperacillin-tazobactam concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured piperacillin-tazobactam concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.

  9/2016 - 12/2021

• Pharmacokinetics of ceftazidim in patients undergoing intermittent hemodialysis

  Population pharmacokinetic modeling is performed based on the measured ceftazidim concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured ceftazidim concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.

  9/2016 - 12/2021

Secondary Outcomes (5)

• Dialyser extraction rate of vancomycin

  9/2016 - 12/2021

• Dialyser extraction rate of teicoplanin

  9/2016 - 12/2021

• Dialyser extraction rate of amoxicillin-clavulanic acid

  9/2016 - 12/2021

• Dialyser extraction rate of piperacillin-tazobactam

  9/2016 - 12/2021

• Dialyser extraction rate of ceftazidim

  9/2016 - 12/2021

Study Arms (5)

Hemodialysis patients on amoxicillin-clavulanic acid

The antibiotic administration protocol is not changed for this study. From the first administration on, administrations (dosage and duration) are well documented. Blood samples are taken as peak, distribution and trough samples during at least 24 or 48 hours. During the first dialysis session after study start, blood samples are also taken from the arterial and venous blood line simultaneously and at different dialysis time points, to calculate dialyzer extraction ratio. When appropriate, urine is collected during a documented period. During the second dialysis after study start, arterial and venous samples are taken for different dialysis settings, in order to calculate extraction ratios for different settings. All blood and urine samples are analyzed for amoxicillin-clavulanic acid.

Other: Blood and urine sampling

Hemodialysis patients on ceftazidim

The antibiotic administration protocol is not changed for this study. From the first administration on, administrations (dosage and duration) are well documented. Blood samples are taken as peak, distribution and trough samples during at least 24 or 48 hours. During the first dialysis session after study start, blood samples are also taken from the arterial and venous blood line simultaneously and at different dialysis time points, to calculate dialyzer extraction ratio. When appropriate, urine is collected during a documented period. During the second dialysis after study start, arterial and venous samples are taken for different dialysis settings, in order to calculate extraction ratios for different settings. All blood and urine samples are analyzed for ceftazidim.

Other: Blood and urine sampling

Hemodialysis patients on piperacillin-tazobactam

The antibiotic administration protocol is not changed for this study. From the first administration on, administrations (dosage and duration) are well documented. Blood samples are taken as peak, distribution and trough samples during at least 24 or 48 hours. During the first dialysis session after study start, blood samples are also taken from the arterial and venous blood line simultaneously and at different dialysis time points, to calculate dialyzer extraction ratio. When appropriate, urine is collected during a documented period. During the second dialysis after study start, arterial and venous samples are taken for different dialysis settings, in order to calculate extraction ratios for different settings. All blood and urine samples are analyzed for piperacillin-tazobactam.

Other: Blood and urine sampling

Hemodialysis patients on vancomycin

The antibiotic administration protocol is not changed for this study. From the first administration on, administrations (dosage and duration) are well documented. Blood samples are taken as peak, distribution and trough samples during at least 24 or 48 hours. During the first dialysis session after study start, blood samples are also taken from the arterial and venous blood line simultaneously and at different dialysis time points, to calculate dialyzer extraction ratio. When appropriate, urine is collected during a documented period. During the second dialysis after study start, arterial and venous samples are taken for different dialysis settings, in order to calculate extraction ratios for different settings. All blood and urine samples are analyzed for vancomycin.

Other: Blood and urine sampling

Hemodialysis patients on teicoplanin

The antibiotic administration protocol is not changed for this study. From the first administration on, administrations (dosage and duration) are well documented. Blood samples are taken as peak, distribution and trough samples during at least 24 or 48 hours. During the first dialysis session after study start, blood samples are also taken from the arterial and venous blood line simultaneously and at different dialysis time points, to calculate dialyzer extraction ratio. When appropriate, urine is collected during a documented period. During the second dialysis after study start, arterial and venous samples are taken for different dialysis settings, in order to calculate extraction ratios for different settings. All blood and urine samples are analyzed for teicoplanin.

Other: Blood and urine sampling

Interventions

Blood and urine sampling OTHER

During a period of maximum 6 days blood is sampled at different time points and urine is collected during documented time intervals.

Hemodialysis patients on amoxicillin-clavulanic acid; Hemodialysis patients on ceftazidim; Hemodialysis patients on piperacillin-tazobactam; Hemodialysis patients on teicoplanin; Hemodialysis patients on vancomycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Per antibiotic agent, up to 30 patients are included. The final needed number is anticipated by the numer of smamples per patient and the pharmacokinetic modeling.

You may qualify if:

• patients with end-stage kidney disease, requiring intermittent hemodialysis
• patient receiving antibiotic treatment for documented or presumed infection (vancomycin, teicoplanin, amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidim)

You may not qualify if:

• pregnant woman
• absence of written informed consent from the patient
• known hypersensitivity or contra-indication to glycopeptides or beta-lactam antibiotics

Sponsors & Collaborators

• University Hospital, Ghent: lead
• University Ghent: collaborator

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Sampling of blood and urine.

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Wim Van Biesen, PhD, MD

  University Hospital, Ghent

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: April 10, 2019
• Study Start: September 15, 2016
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: November 29, 2022

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)