Clinical trial NCT04033029: Antibiotic Plasma Concentrations During Continuous Renal Replacement Therapy With a High Adsorption Membrane (oXiris®)
Official title: Antibiotic Plasma Concentrations During Continuous Renal Replacement Therapy With a High Adsorption Membrane (oXiris®)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemodiafiltration
Sepsis
Acute Kidney Injury
Keywords: Acute kidney Injury
Sepsis
Antibiotic plasma level
CRRT
oXiris®
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
First posted: 2019-07-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

Brief summary: * 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of individuals attaining a defined pharmacokinetic-pharmacodynamic target for antimicrobial therapy
timeFrame: 01/08/2019 - 31/12/2021
Secondary outcomes:
measure: Antibiotic concentration-time data.
timeFrame: 01/08/2019 - 31/12/2021
measure: Blood flow (mL/min). CRRT covariate that can affect drug exposure and PK parameters.
timeFrame: 01/08/2019 - 31/12/2021
measure: Dialysate flow rate (L/h).
timeFrame: 01/08/2019 - 31/12/2021
measure: Ultrafiltrate flow rate (L/h).
timeFrame: 01/08/2019 - 31/12/2021
measure: Replacement fluid (mL/h).
timeFrame: 01/08/2019 - 31/12/2021
measure: Extraction rate (L/h).
timeFrame: 01/08/2019 - 31/12/2021
measure: Urine output (mL/day).
timeFrame: 01/08/2019 - 31/12/2021
measure: Albumin (g/L).
timeFrame: 01/08/2019 - 31/12/2021
measure: Weight (Kg).
timeFrame: 01/08/2019 - 31/12/2021
measure: Admission diagnosis: surgical, medical, trauma.
timeFrame: 01/08/2019 - 31/12/2021
measure: Dosage (mg, frequency of administration and mode of administration) needed to achieve the PK/PD target.
timeFrame: 01/08/2019 - 31/12/2021
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Helena Colom Codina
Study officials:
affiliation: Universitat Autònoma de Barcelona
name: Helena Colom Codina, Phd
role: PRINCIPAL_INVESTIGATOR
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