Pharmacokinetics of Antibiotics in Critically Ill Patients Receiving CVVHF
- Conditions
- Acute Kidney InjurySepsis
- Interventions
- Other: blood samples and filtered fluid will be collected.
- Registration Number
- NCT04800952
- Lead Sponsor
- Osaka University
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 120
- 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
- Chronic renal failure
- Obvious or suspected pregnancy
- Intracranial bleeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description To establish the appropriate dosing regimens of newly available antibiotics during CRRT blood samples and filtered fluid will be collected. 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.
- Primary Outcome Measures
Name Time Method Plasma new antibiotics concentration during continuous venovenous haemofiltration (CVVHF) in critically ill patients receiving infusion of these drugs. 72 hours 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. 72 hours 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
Name Time Method Concentration of serum creatinine through study completion, an average of 1 year Concentration of serum creatinine
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 length of stay in the hospital
ICU Mortality at ICU discharge assessed up to 30 days Mortality at ICU discharge
Hospital Mortality at hospital discharge assessed up to 30 days Mortality at hospital discharge