- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05426499
Translational PKPD Modeling of Anti-infective Drugs Used in Pediatric Units.
Translational PKPD Modeling of Anti-infective Drugs in Children Treated in Pediatric Units on the Example of Selected Antibiotics and Antifungals.
Study Overview
Status
Conditions
Detailed Description
Cefotaxime and meropenem are broad-spectrum antibiotics, most commonly prescribed in pediatric and adult intensive care units. Unfortunately, the applied dosing regimens based on the results obtained in adults or only on drug pharmacokinetics (without taking into account the pharmacodynamic profile) often fail. The situation is additionally complicated by the observed clinically significant drug interactions. The results of published studies indicate the need to develop PKPD models for these drugs in the pediatric and adult populations. Fluconazole, isavuconazole and anidulafungin are the azole anti-fungal drugs and echinocandin. Despite the optimistic results of studies in adults, showing high efficacy, a favorable PK profile, and the safety profile of these therapeutics, there are no studies in children.
The research will be conducted at the Pediatric Clinical Hospital of K. Jonscher, The Greater Poland Cancer Center, and Heliodor Święcicki Clinical Hospital of the Medical University in Poznań. With the approval of the Bioethics Committee, about 150 children and adults will be included in the study. Blood samples will be collected at appropriate time points to investigate the PK profile. The measured pharmacological effect will be the minimum inhibitory concentration (MIC). PKPD indices will be included in the model, depending on the tested drug: T> MIC, Cmax / MIC, and AUC / MIC. The values of covariates that may affect drug PK and PD will be reported. The analysis will consider the polymorphisms of the OAT3 organic anion transporter genes and the MRP4 transport protein. HPLC will examine plasma drug concentration levels in conjunction with UV detection. The Xevo TQ-S micro triple quadrupole mass spectrometer, coupled with ultra-efficient liquid chromatography with the PDA acquity UPLC detector I-class PDA Waters. The genetic polymorphism of selected genes will be tested by real-time PCR using the LightCycler® 480 II Instrument. The PKPD population analysis will be performed by nonlinear modeling of mixed-effects using NONMEM version 7.2.0, the GNU Fortran 9.0 compiler, and Wings for NONMEM and RStudio. The collected data will be used to build hypothetical models using neural networks.
The expected result of the project's primary goal is to build PKPD models of fluconazole, isavuconazole, anidulafungin, cefotaxime, and meropenem in the pediatric and adult populations. According to the final model's principles, they will be evaluated and can serve as a specialized tool for personalizing pharmacotherapy.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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Długa 1/2
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Poznań, Długa 1/2, Poland, 61-848
- Szpital Kliniczny im. Heliodora Święcickiego UMP
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Garbary 15
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Poznań, Garbary 15, Poland, 61-866
- Wielkopolskie Centrum Onkologii
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Rokietnicka 7
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Poznań, Rokietnicka 7, Poland, 60-806
- Poznan University of Medical Sciences, Department of Clinical Pharmacy and Biopharmacy
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Szpitalna 27/33
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Poznań, Szpitalna 27/33, Poland, 60-572
- Szpital Kliniczny im. Karola Jonschera Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Obtaining informed consent from the patient/parent of the patient
- A bacterial and fungal infection that requires the use of at least one of the drugs listed based on clinical indications and the attending physician's decision.
Exclusion Criteria:
- Proven allergic reaction to medications used
- No written consent
- Contraindications in SmPC
- Combination therapy with at least two antibacterial drugs and/or at least two antifungal drugs
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Patients requiring cefotaxime treatment
The treatment choice and the recommended dosage will depend on the isolated pathogen.
Therapy will be based on the SmPC of the appropriate drug.
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Dosage according to SmPC
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Patients requiring meropenem treatment
The treatment choice and the recommended dosage will depend on the isolated pathogen.
Therapy will be based on the SmPC of the appropriate drug.
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Dosage according to SmPC
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Patients requiring fluconazole treatment
The treatment choice and the recommended dosage will depend on the isolated pathogen.
Therapy will be based on the SmPC of the appropriate drug.
|
Dosage according to SmPC
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Patients requiring isavuconazole treatment
The treatment choice and the recommended dosage will depend on the isolated pathogen.
Therapy will be based on the SmPC of the appropriate drug.
|
Dosage according to SmPC
|
Patients requiring anidulafungin treatment
The treatment choice and the recommended dosage will depend on the isolated pathogen.
Therapy will be based on the SmPC of the appropriate drug.
|
Dosage according to SmPC
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cefotaxime plasma concentration [ng/ml]
Time Frame: Just before the next dose and at 0.33; 0.66; 1; 2; 4; 6; 8 hours after the start of drug administration
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Measurements of cefotaxime plasma concentrations [ng/ml] before and after dosage of a drug.
Blood samples were collected according to the study protocol.
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Just before the next dose and at 0.33; 0.66; 1; 2; 4; 6; 8 hours after the start of drug administration
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Meropenem plasma concentration [ng/ml]
Time Frame: Just before the next dose and at 1,5; 3; 6; 8 hours after the start of drug administration
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Measurements of meropenem plasma concentrations [ng/ml] before and after dosage of a drug.
Blood samples were collected according to the study protocol.
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Just before the next dose and at 1,5; 3; 6; 8 hours after the start of drug administration
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Fluconazole plasma concentration [ng/ml]
Time Frame: Just before the next dose and at 0,5; 1; 3; 10; 24 hours after the start of drug administration
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Measurements of fluconazole plasma concentrations [ng/ml] before and after dosage of a drug.
Blood samples were collected according to the study protocol.
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Just before the next dose and at 0,5; 1; 3; 10; 24 hours after the start of drug administration
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Isavuconazole plasma concentration [ng/ml]
Time Frame: Just before the next dose and at 0,25; 0,5; 0,75; 1; 1,25; 1,5; 2; 3; 4; 6; 8; 10; 12; 14; 16; 24 hours after the start of drug administration
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Measurements of isavuconazole plasma concentrations [ng/ml] before and after dosage of a drug.
Blood samples were collected according to the study protocol.
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Just before the next dose and at 0,25; 0,5; 0,75; 1; 1,25; 1,5; 2; 3; 4; 6; 8; 10; 12; 14; 16; 24 hours after the start of drug administration
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Anidulafungin plasma concentration [ng/ml]
Time Frame: Just before the next dose and at 0,5; 1; 1,5; 2; 4; 6; 8; 10; 12; 24 hours after the start of drug administration
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Measurements of anidulafungin plasma concentrations [ng/ml] before and after dosage of a drug.
Blood samples were collected according to the study protocol.
|
Just before the next dose and at 0,5; 1; 1,5; 2; 4; 6; 8; 10; 12; 24 hours after the start of drug administration
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Minimum inhibitory concentration
Time Frame: On the first day after patient inclusion.
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The lowest concentration (in μg/mL) of an antibiotic that inhibits the growth of a given strain of bacteria.
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On the first day after patient inclusion.
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Plasma creatinine concentration
Time Frame: On the first and sixth day after patient inclusion.
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Measurement of creatinine concentrations in blood and urine.
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On the first and sixth day after patient inclusion.
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Creatinine clearance (CrCl)
Time Frame: On the first and sixth day after patient inclusion.
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Calculation of creatinine clearance (CrCl) based on measurement of creatinine concentration.
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On the first and sixth day after patient inclusion.
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Estimated GFR (eGFR)
Time Frame: On the first and sixth day after patient inclusion.
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Calculation of estimated GFR (eGFR) based on measurement of creatinine concentration.
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On the first and sixth day after patient inclusion.
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Bilirubin concentration
Time Frame: On the first and sixth day after patient inclusion.
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Measurement of bilirubin concentration
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On the first and sixth day after patient inclusion.
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Albumin concentration
Time Frame: On the first and sixth day after patient inclusion.
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Measurement of albumin concentration
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On the first and sixth day after patient inclusion.
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AST concentration
Time Frame: On the first and sixth day after patient inclusion.
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Measurement of AST concentration
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On the first and sixth day after patient inclusion.
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ALT concentration
Time Frame: On the first and sixth day after patient inclusion.
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Measurement of ALT concentration
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On the first and sixth day after patient inclusion.
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GGT concentration
Time Frame: On the first and sixth day after patient inclusion.
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Measurement of GGT concentration
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On the first and sixth day after patient inclusion.
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ALP concentration
Time Frame: On the first and sixth day after patient inclusion.
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Measurement of ALP concentration
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On the first and sixth day after patient inclusion.
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Collaborators and Investigators
Investigators
- Principal Investigator: Agnieszka Bienert, MSC,PhD, Poznan University of Medical Sciences
- Principal Investigator: Alicja Bartkowska-Śniatkowska, MD, PhD, Poznan University of Medical Sciences
- Study Chair: William J. Jusko, PhD, School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Anti-Bacterial Agents
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors
- Meropenem
- Anidulafungin
- Fluconazole
- Isavuconazole
- Cefotaxime
- Cefoxitin
Other Study ID Numbers
- 820/21
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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