Pharmacokinetics of Antibiotics in Critically Ill Patients Receiving CVVHF

Pharmacokinetics of New Licensed Antibiotics in Critically Ill Patients Receiving Continuous Venovenous Haemofiltration: An International Collaborative Study

The mortality in patients with sepsis and severe acute kidney injury requiring continuous renal replacement therapy (CRRT) remains high. Antibiotic therapy is a key treatment of these patients and in recent years new antibiotics have been licensed. However, data is lacking to determine the optimal dosing regimens of these antibiotics for high (Australia and other countries) and low intensity (Japan) of CRRT.

Aim To establish the appropriate dosing regimens of newly available antibiotics during CRRT can applied globally.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Acute Kidney Injury
• Intervention / Treatment: Other: blood samples and filtered fluid will be collected.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Naoya Iguchi, MD, PhD; Phone Number: +81 6 6879 3133; Email: iguchi@hp-icu.med.osaka-u.ac.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (age ≥18 years or older)
• Sepsis (Sepsis-3 criteria)
• Acute kidney injury requiring CRRT (KDIGO criteria)
• Eligible for intensive care without restrictions or limitations

Exclusion Criteria:

• Chronic renal failure
• Obvious or suspected pregnancy
• Intracranial bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: To establish the appropriate dosing regimens of newly available antibiotics during CRRT; High dose (world standard dose) and low dose CRRT (Japan local) CRRT protocol Vascular access will be obtained by inserting a double-lumen dialysis catheter into the internal jugular or femoral veins. High dose CRRT in Australia, Blood flow through the extracorporeal circuit will be maintained at 150 ml/min. The CVVHF replacement volume will be set at 25ml/kg/hour and bicarbonate-buffered replacement fluids will be added in post-dilutional mode. Low dose CRRT in Japan, Blood flow through the extracorporeal circuit will be maintained at 80 ml/min. CVVHF replacement volume will be set at 15ml/kg/hour and bicarbonate-buffered replacement fluids will be added in the post-dilutional mode. Fluid balance, volume removal and the duration of CVVHF will be determined by the ICU physician based on the patient's individual clinical status.

Other: blood samples and filtered fluid will be collected.; Arterial blood samples will be collected just before the commencement of continuous venovenous haemofiltration (CVVHF) and 1 h after the termination of CVVHF. Prefilter and post-filter venous blood samples and filtered fluid will be collected 1 and 3 h after the commencement of CVVHF and at the end of CVVHF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma new antibiotics concentration during continuous venovenous haemofiltration (CVVHF) in critically ill patients receiving infusion of these drugs.	New drugs are Tedizolid, Daptomycin (anti-MRSA), Tazobactam/ Ceftolozane (anti-gram negative), Metronidazole (Anti-anaerobic). Plasma antibiotics concentrations will be measured at 5 time-points and prefilter and postfilter plasma and filtered-fluid antibiotics levels will be measured at 3 time-points during CVVHF.	72 hours
Calculated clearances of new antibiotics during continuous venovenous haemofiltration (CVVHF) in critically ill patients receiving infusion of these drugs.	New drugs are Tedizolid, Daptomycin (anti-MRSA), Tazobactam/ Ceftolozane (anti-gram negative), Metronidazole (Anti-anaerobic). Total clearance by CVVHF: (Cltotal) = (Cpre - Cpost / Cpre) × Blood flow (ml/min), Clearance by filtration: (Clfil) = (Clfil / Cpre)× replacement volume (ml/min), Clearance by absorption of the filter: (Clab) = (Cltotal) - (Clfil) (ml/min).	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of serum creatinine	Concentration of serum creatinine	through study completion, an average of 1 year
length of stay in the hospital	length of stay in the hospital	up to 30 days, length of stay in the hospital will be calculated using the earliest of date that the subject is medically ready for discharge when captured, the date of discharge
ICU Mortality	Mortality at ICU discharge	at ICU discharge assessed up to 30 days
Hospital Mortality	Mortality at hospital discharge	at hospital discharge assessed up to 30 days

Collaborators and Investigators

• Sponsor: Osaka University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: January 24, 2021
• First Submitted That Met QC Criteria: March 14, 2021
• First Posted (Actual): March 16, 2021

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: 20235

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No