Back to resultsPharmacokinetics of Antibiotics in Critically Ill Patients Receiving CVVHF
Primary Purpose
Sepsis, Acute Kidney Injury
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
blood samples and filtered fluid will be collected.
Sponsored by
About this trial
This is an interventional other trial for Sepsis
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
To establish the appropriate dosing regimens of newly available antibiotics during CRRT
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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).
Secondary Outcome Measures
Concentration of serum creatinine
Concentration of serum creatinine
length of stay in the hospital
length of stay in the hospital
ICU Mortality
Mortality at ICU discharge
Hospital Mortality
Mortality at hospital discharge
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04800952
Brief Title
Pharmacokinetics of Antibiotics in Critically Ill Patients Receiving CVVHF
Official Title
Pharmacokinetics of New Licensed Antibiotics in Critically Ill Patients Receiving Continuous Venovenous Haemofiltration: An International Collaborative Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 2021 (Anticipated)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
April 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Osaka University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Acute Kidney Injury
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
To establish the appropriate dosing regimens of newly available antibiotics during CRRT
Arm Type
Other
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
blood samples and filtered fluid will be collected.
Intervention Description
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.
Primary Outcome Measure Information:
Title
Plasma new antibiotics concentration during continuous venovenous haemofiltration (CVVHF) in critically ill patients receiving infusion of these drugs.
Description
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.
Time Frame
72 hours
Title
Calculated clearances of new antibiotics during continuous venovenous haemofiltration (CVVHF) in critically ill patients receiving infusion of these drugs.
Description
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).
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
Concentration of serum creatinine
Description
Concentration of serum creatinine
Time Frame
through study completion, an average of 1 year
Title
length of stay in the hospital
Description
length of stay in the hospital
Time Frame
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
Title
ICU Mortality
Description
Mortality at ICU discharge
Time Frame
at ICU discharge assessed up to 30 days
Title
Hospital Mortality
Description
Mortality at hospital discharge
Time Frame
at hospital discharge assessed up to 30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Naoya Iguchi, MD, PhD
Phone
+81 6 6879 3133
Email
iguchi@hp-icu.med.osaka-u.ac.jp
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Pharmacokinetics of Antibiotics in Critically Ill Patients Receiving CVVHF
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