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

NCT ID: NCT04033029

Last Updated: 2023-10-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

20 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-01-01

Study Completion Date

2023-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

* 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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hemodiafiltration Sepsis Acute Kidney Injury

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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).

Continuous venovenous hemodiafiltration with high adsorption membrane (oXiris®)

Intervention Type DEVICE

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).

Antibiotics

Intervention Type DRUG

Antibiotic concentration-time data will be collected and analyzed.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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).

Intervention Type DEVICE

Antibiotics

Antibiotic concentration-time data will be collected and analyzed.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Piperacillin/tazobactam Ceftazidime Cefepime Daptomycin Ceftolozane/tazobactam

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role collaborator

Hospital Universitari de Bellvitge

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Helena Colom Codina

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Helena Colom Codina, Phd

Role: PRINCIPAL_INVESTIGATOR

Universitat Autònoma de Barcelona

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Helena Colom Codina

Barcelona, , Spain

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Spain

References

Explore related publications, articles, or registry entries linked to this study.

Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y, Reinhart K; EPIC II Group of Investigators. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009 Dec 2;302(21):2323-9. doi: 10.1001/jama.2009.1754.

Reference Type BACKGROUND
PMID: 19952319 (View on PubMed)

Brun-Buisson C. The epidemiology of the systemic inflammatory response. Intensive Care Med. 2000;26 Suppl 1(Suppl 1):S64-74. doi: 10.1007/s001340051121.

Reference Type BACKGROUND
PMID: 10786961 (View on PubMed)

Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999 Feb;115(2):462-74. doi: 10.1378/chest.115.2.462.

Reference Type BACKGROUND
PMID: 10027448 (View on PubMed)

Zaragoza R, Artero A, Camarena JJ, Sancho S, Gonzalez R, Nogueira JM. The influence of inadequate empirical antimicrobial treatment on patients with bloodstream infections in an intensive care unit. Clin Microbiol Infect. 2003 May;9(5):412-8. doi: 10.1046/j.1469-0691.2003.00656.x.

Reference Type BACKGROUND
PMID: 12848754 (View on PubMed)

Pinder M, Bellomo R, Lipman J. Pharmacological principles of antibiotic prescription in the critically ill. Anaesth Intensive Care. 2002 Apr;30(2):134-44. doi: 10.1177/0310057X0203000203.

Reference Type BACKGROUND
PMID: 12002919 (View on PubMed)

Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000 Jul;118(1):146-55. doi: 10.1378/chest.118.1.146.

Reference Type BACKGROUND
PMID: 10893372 (View on PubMed)

Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998 Jan;26(1):1-10; quiz 11-2. doi: 10.1086/516284.

Reference Type BACKGROUND
PMID: 9455502 (View on PubMed)

Roberts JA, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Piperacillin penetration into tissue of critically ill patients with sepsis--bolus versus continuous administration? Crit Care Med. 2009 Mar;37(3):926-33. doi: 10.1097/CCM.0b013e3181968e44.

Reference Type BACKGROUND
PMID: 19237898 (View on PubMed)

Heinemeyer G, Link J, Weber W, Meschede V, Roots I. Clearance of ceftriaxone in critical care patients with acute renal failure. Intensive Care Med. 1990;16(7):448-53. doi: 10.1007/BF01711224.

Reference Type BACKGROUND
PMID: 2269714 (View on PubMed)

Trotman RL, Williamson JC, Shoemaker DM, Salzer WL. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005 Oct 15;41(8):1159-66. doi: 10.1086/444500. Epub 2005 Sep 12.

Reference Type BACKGROUND
PMID: 16163635 (View on PubMed)

Carcelero San Martin E, Soy Muner D. [Dosage of antipseudomonal antibiotics in patients with acute kidney injury subjected to continuous renal replacement therapies]. Med Intensiva. 2013 Apr;37(3):185-200. doi: 10.1016/j.medin.2012.02.012. Epub 2012 Apr 3. Spanish.

Reference Type BACKGROUND
PMID: 22475763 (View on PubMed)

Matzke GR, Frye RF, Joy MS, Palevsky PM. Determinants of ceftazidime clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis. Antimicrob Agents Chemother. 2000 Jun;44(6):1639-44. doi: 10.1128/AAC.44.6.1639-1644.2000.

Reference Type BACKGROUND
PMID: 10817721 (View on PubMed)

Bauer SR, Salem C, Connor MJ Jr, Groszek J, Taylor ME, Wei P, Tolwani AJ, Fissell WH. Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Clin J Am Soc Nephrol. 2012 Mar;7(3):452-7. doi: 10.2215/CJN.10741011. Epub 2012 Jan 26.

Reference Type BACKGROUND
PMID: 22282479 (View on PubMed)

Valtonen M, Tiula E, Backman JT, Neuvonen PJ. Elimination of meropenem during continuous veno-venous haemofiltration and haemodiafiltration in patients with acute renal failure. J Antimicrob Chemother. 2000 May;45(5):701-4. doi: 10.1093/jac/45.5.701.

Reference Type BACKGROUND
PMID: 10797097 (View on PubMed)

Roberts DM, Roberts JA, Roberts MS, Liu X, Nair P, Cole L, Lipman J, Bellomo R; RENAL Replacement Therapy Study Investigators. Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study. Crit Care Med. 2012 May;40(5):1523-8. doi: 10.1097/CCM.0b013e318241e553.

Reference Type BACKGROUND
PMID: 22511133 (View on PubMed)

Seyler L, Cotton F, Taccone FS, De Backer D, Macours P, Vincent JL, Jacobs F. Recommended beta-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy. Crit Care. 2011;15(3):R137. doi: 10.1186/cc10257. Epub 2011 Jun 6.

Reference Type RESULT
PMID: 21649882 (View on PubMed)

Rigo-Bonnin R, Ribera A, Arbiol-Roca A, Cobo-Sacristan S, Padulles A, Murillo O, Shaw E, Granada R, Perez-Fernandez XL, Tubau F, Alia P. Development and validation of a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of beta-lactam antibiotic concentration in human plasma. Clin Chim Acta. 2017 May;468:215-224. doi: 10.1016/j.cca.2017.03.009. Epub 2017 Mar 10.

Reference Type RESULT
PMID: 28288784 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

HCC-PIP-2018-01

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

SIRAKI 02 Posthoc Analysis.
NCT06781294 ACTIVE_NOT_RECRUITING NA
TIMP2*IGFBP7 and Transient AKI
NCT03472079 RECRUITING