Pharmacokinetics of Antibiotics in Critically Ill Patients Receiving CVVHF

NCT04800952 | Unknown

• 1 other identifier: 20235
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Sepsis; Acute Kidney Injury

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Concentration of serum creatinine

  through study completion, an average of 1 year

• 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

  at ICU discharge assessed up to 30 days

• Hospital Mortality

  at hospital discharge assessed up to 30 days

Study Arms (1)

To establish the appropriate dosing regimens of newly available antibiotics during CRRT

OTHER

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.

Interventions

blood samples and filtered fluid will be collected. OTHER

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.

To establish the appropriate dosing regimens of newly available antibiotics during CRRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Osaka University: lead

MeSH Terms

Conditions

Sepsis; Acute Kidney Injury

Interventions

Blood Specimen Collection

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)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Naoya Iguchi, MD, PhD

CONTACT

+81 6 6879 3133; iguchi@hp-icu.med.osaka-u.ac.jp

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2021
• First Posted: March 16, 2021
• Study Start: April 1, 2021
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2023
• Last Updated: March 19, 2021

Record last verified: 2021-03