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

NCT04033029 | Completed DMC FDA Drug FDA Device

• 1 other identifier: HCC-PIP-2018-01
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemodiafiltration; Sepsis; Acute Kidney Injury

Keywords

Acute kidney Injury; Sepsis; Antibiotic plasma level; CRRT; oXiris®

Outcome Measures

Primary Outcomes (1)

• Number of individuals attaining a defined pharmacokinetic-pharmacodynamic target for antimicrobial therapy

  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 Outcomes (11)

• Antibiotic concentration-time data.

  01/08/2019 - 31/12/2021

• Blood flow (mL/min). CRRT covariate that can affect drug exposure and PK parameters.

  01/08/2019 - 31/12/2021

• Dialysate flow rate (L/h).

  01/08/2019 - 31/12/2021

• Ultrafiltrate flow rate (L/h).

  01/08/2019 - 31/12/2021

• Replacement fluid (mL/h).

  01/08/2019 - 31/12/2021

Study Arms (1)

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®); Drug: Antibiotics

Interventions

Continuous venovenous hemodiafiltration with high adsorption membrane (oXiris®) 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).

Patients under CVVHDF with high adsorption membrane

Antibiotics DRUG

Antibiotic concentration-time data will be collected and analyzed.

Also known as: Piperacillin/tazobactam, Ceftazidime, Cefepime, Daptomycin, Ceftolozane/tazobactam

Patients under CVVHDF with high adsorption membrane

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

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.

You may qualify if:

• 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.

Sponsors & Collaborators

• Hospital Universitari de Bellvitge: lead
• Baxter Healthcare Corporation: collaborator

Study Sites (1)

Helena Colom Codina

Barcelona, Spain

Location

Related Publications (17)

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• 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.

  PMID: 22475763 BACKGROUND

• 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.

  PMID: 10817721 BACKGROUND

• 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.

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• 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.

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• 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.

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• 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.

  PMID: 21649882 RESULT

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  PMID: 28288784 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, ultrafiltrate and urine samples.

MeSH Terms

Conditions

Sepsis; Acute Kidney Injury

Interventions

Continuous Renal Replacement Therapy; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination; Ceftazidime; Cefepime; Daptomycin; ceftolozane, tazobactam drug combination

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Cephaloridine; Cephalosporins; Thiazines; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Helena Colom Codina, Phd

  Universitat Autònoma de Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: July 25, 2019
• Study Start: January 1, 2021
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)