Antibiotic Plasma Concentrations During Continuous Renal Replacement Therapy With a High Adsorption Membrane (oXiris®)

October 5, 2023 updated by: Helena Colom Codina, Hospital Universitari de Bellvitge
  • Study: Open label, non-randomized, observational, descriptive and prospective pharmacokinetic.
  • Patients: sepsis patients undergoing continuous renal replacement therapy (CRRT) and admitted at the Intensive care unit of Bellvitge University Hospitals. No power calculations needed.
  • Antibiotic treatment: piperacillin, ceftazidime, cefepime, ceftolozane and daptomycin as their standard of care and doses will be at the discretion of the treating physician.
  • CRRT treatment: continuous venovenous hemodiafiltration (CVVHDF) will be performed by using the PrismafleX eXeed™ system with a high adsorbent membrane (oXiris®).
  • Antibiotic concentrations: blood pre and post filter, urine and ultrafiltrate samples will be collected at steady state conditions. Samplig time will depend on dosage regimens of each antibiotic.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study is an open label, non-randomized, observational, descriptive and prospective pharmacokinetic study.

Setting: this study will be conducted at the Intensive Care Unit at the Bellvitge University Hospital.

Study aims: the primary objective is to determine the PK/PD target attainment of piperacillin, ceftazidime, cefepime, ceftolozane and daptomycin in septic critically ill patients treated with CVVHDF using oXiris® membrane. Secondary aims are: i) to characterize the PK of piperacillin, ceftazidime, cefepime, ceftolozane and daptomycin in critically ill patients under CVVHDF therapy using oXiris® membrane by developing a population PK model; ii) to identify the clinical and demographic sources of PK variability observed in these patient and iii) to develop individualized dosing recommendations based on the PK/PD index associated with therapy success.

Recruitment process: patients who meet the inclusion criteria will be enrolled for at least 72 hours (maximum 96 hours).

Sample size: no power calculations are required for this study as it aims to investigate the PK of these antibiotics and does not intend to measure the effect of an intervention between two groups.

Antibiotic treatment: patients will receive piperacillin, ceftazidime, cefepime, ceftolozane/tazobactam or daptomycin as their standard of care. Doses will be at the discretion of the treating physician. At the same time, patients will be treated under continuous renal replacement techniques (CRRT) with continuous venovenous hemodiafiltration mode (CVVHDF) using PrismafleX eXeed™ system and high adsorbent polyethyleneimide membrane (oXiris®). Filtration parameters will be determined following the local protocol (dose of 25-30 ml/kg/h) CRRT initiation will be determined by the treating physician on charge, according with the current recommendations of clinical practice and prescriptions of CRRT and local management protocols. The decision to stop the treatment will be determined by:

  • Adequate renal recovery status: adequate capacity to effectively maintain fluid and electrolyte homeostasis and urinary output (>450 ml in 24 h) without the use of diuretics.
  • Hemodynamic stability without renal function recovery. Therapy will be continued as intermittent hemodialysis.

Antibiotic concentrations: blood, either pre and post filtration through oXiris® membrane, urine and ultrafiltrate samples will be obtained. Samples will be collected at 1) steady state conditions and 2) after minimum 24h from the concomitant administration of CRRT and antibiotic for piperacillin, ceftazidime, cefepime, ceftolozane and 48h for daptomycin. Sampling times will depend on the dosage regimen of each antibiotic therapy. Drug concentrations will be determined using a previously developed and validated measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry.

Study Type

Observational

Enrollment (Actual)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Barcelona, Spain
        • Helena Colom Codina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Critically ill patients under continuous venovenous hemodiafiltration (CVVHDF) by using the PrismafleX eXeed™ system with a high adsorbent membrane (oXiris®) and requiring antibiotic treatment with: piperacillin, ceftazidime, cefepime, ceftolozane/tazobactam or daptomycin.

Description

Inclusion Criteria:

  • Patients in the setting of sepsis and requirements of CRRT with high adsorption membranes for at least 48 h
  • Age >18 years
  • Treatment with piperacillin, ceftazidime, cefepime, ceftolozane and daptomycin prescribed at the discretion of the treating intensive care physician.
  • Written informed consent will be required before the inclusion of a patient whenever possible and will be requested from the nearest relatives in the other cases.

Exclusion Criteria: none.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients under CVVHDF with high adsorption membrane
Continuous venovenous hemodiafiltration mode (CVVHDF) using PrismafleX eXeed™ system and high adsorbent polyethyleneimide membrane (oXiris®). Filtration parameters will be determined following the local protocol (dose of 25-30 ml/kg/h).
Device: Continuous venovenous hemodiafiltration with high adsorption membrane (oXiris®)
CRRT initiation will be determined by the treating physician on charge, according with the current recommendations of clinical practice and prescriptions of CRRT and local management protocols. The CVVHDF mode will be performed by using PrismafleX eXeed™ system and high adsorbent polyethyleneimide membrane (oXiris®). Filtration parameters will be determined following the local protocol (dose of 25-30 ml/kg/h).
Drug: Antibiotics
Antibiotic concentration-time data will be collected and analyzed.
Other Names:
  • Daptomycin
  • Cefepime
  • Ceftazidime
  • Piperacillin/tazobactam
  • Ceftolozane/tazobactam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of individuals attaining a defined pharmacokinetic-pharmacodynamic target for antimicrobial therapy
Time Frame: 01/08/2019 - 31/12/2021
Time above minimum inhibitory concentration (%fT > k× MIC) for betalactams, and total-drug AUC24/MIC ≥ 666 for daptomycin
01/08/2019 - 31/12/2021

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Antibiotic concentration-time data.
Time Frame: 01/08/2019 - 31/12/2021
Antibiotic concentration-time data will be collected and analysed to characterize the PK profile of piperacillin, ceftazidime, cefepime, ceftolozane and daptomycin in critically ill patients under CRRT therapy using oXiris® membrane and a population PK model will be developed.
01/08/2019 - 31/12/2021
Blood flow (mL/min). CRRT covariate that can affect drug exposure and PK parameters.
Time Frame: 01/08/2019 - 31/12/2021
Effect of CRRT settings, physiopathological and demographic data on drug exposure and PK parameters.
01/08/2019 - 31/12/2021
Dialysate flow rate (L/h).
Time Frame: 01/08/2019 - 31/12/2021
CRRT covariate that can affect drug exposure and PK parameters. For each antibiotic, a population pharmacokinetic model will be developed.
01/08/2019 - 31/12/2021
Ultrafiltrate flow rate (L/h).
Time Frame: 01/08/2019 - 31/12/2021
CRRT covariate that can affect drug exposure and PK parameters. For each antibiotic, a population pharmacokinetic model will be developed.
01/08/2019 - 31/12/2021
Replacement fluid (mL/h).
Time Frame: 01/08/2019 - 31/12/2021
CRRT covariate that can affect drug exposure and PK parameters. For each antibiotic, a population pharmacokinetic model will be developed.
01/08/2019 - 31/12/2021
Extraction rate (L/h).
Time Frame: 01/08/2019 - 31/12/2021
CRRT covariate that can affect drug exposure and PK parameters. For each antibiotic, a population pharmacokinetic model will be developed.
01/08/2019 - 31/12/2021
Urine output (mL/day).
Time Frame: 01/08/2019 - 31/12/2021
Physiopathological variables that can affect drug exposure and PK parameters. For each antibiotic, a population pharmacokinetic model will be developed.
01/08/2019 - 31/12/2021
Albumin (g/L).
Time Frame: 01/08/2019 - 31/12/2021
Physiopathological variables that can affect drug exposure and PK parameters. For each antibiotic, a population pharmacokinetic model will be developed.
01/08/2019 - 31/12/2021
Weight (Kg).
Time Frame: 01/08/2019 - 31/12/2021
Physiopathological variables that can affect drug exposure and PK parameters. For each antibiotic, a population pharmacokinetic model will be developed.
01/08/2019 - 31/12/2021
Admission diagnosis: surgical, medical, trauma.
Time Frame: 01/08/2019 - 31/12/2021
Physiopathological variables that can affect drug exposure and PK parameters. For each antibiotic, a population pharmacokinetic model will be developed.
01/08/2019 - 31/12/2021
Dosage (mg, frequency of administration and mode of administration) needed to achieve the PK/PD target.
Time Frame: 01/08/2019 - 31/12/2021
Monte-Carlo Simulations using the population PK parameters of the final models in order to generate concentration-time profiles of n hypothetical subjects per dosing regimen will be performed. With this data, we will calculate the probability of target attainment of the PK/PD indices associated to antibiotic therapy success, which will translate in the development of individualized dosing recommendations for our patient population.
01/08/2019 - 31/12/2021

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitari de Bellvitge

Collaborators

Baxter Healthcare Corporation

Investigators

  • Principal Investigator: Helena Colom Codina, Phd, Universitat Autonoma de Barcelona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2021

Primary Completion (Actual)

June 30, 2023

Study Completion (Actual)

June 30, 2023

Study Registration Dates

First Submitted

February 20, 2019

First Submitted That Met QC Criteria

July 24, 2019

First Posted (Actual)

July 25, 2019

Study Record Updates

Last Update Posted (Estimated)

October 9, 2023

Last Update Submitted That Met QC Criteria

October 5, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCC-PIP-2018-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

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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