Study of Ceftazidime-Avibactam Blood Concentrations in Intensive Care Unit Patients With Renal Failure Requiring Continuous Dialysis

Study Overview
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Brief Summary
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The study's primary objective is to determine plasma and dialysis fluid concentrations in patients prescribed ceftazidime-avibactam as the standard treatment for their infection and requiring continuous venovenous hemodiafiltration (CVVHDF) as part of the standard treatment for acute or chronic renal failure. Secondarily, the study will evaluate the pharmacokinetics of ceftazidime-avibactam in these patients on CVVHDF. The study will also determine if the prescribed dose meets pharmacodynamic targets.

Official Title
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: Pharmacokinetics of Ceftazidime-Avibactam in Critically Ill Patients With Renal Failure Requiring Continuous Venovenous Hemodiafiltration

Conditions
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Renal Failure, Bacterial Infections, Critical Illness

Intervention / Treatment
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* Drug: Ceftazidime-avibactam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults > 18 years of age Patients requiring continuous renal replacement therapy (CRRT) due to acute or chronic renal failure documented or suspected infection requiring a prescription for ceftazidime-avibactam Exclusion Criteria: Patients on CRRT < 24 hours Patients on ceftazidime-avibactam < 24 hours Patients unable to remain on CRRT for 32 hours continuously without clotting

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ceftazidime and Avibactam<br>Ceftazidime-avibactam pharmacokinetic monitoring | Drug: Ceftazidime-avibactam<br>* Patients will be started on 2.5 gm IV every 8 hours<br>* Other names: Avycaz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ceftazidime plasma concentrations | mg/L | At hours post dose: 0, 2, 3, 4, 6, 8 on or after Day 2 of therapy (i.e. during the fourth dose) | 
| Avibactam plasma concentrations | mg/L | At hours post dose: 0, 2, 3, 4, 6, 8 on or after Day 2 of therapy (i.e. during the fourth dose) | 
| Ceftazidime effluent concentrations | mg/L | At hours post dose: 0, 2, 3, 4, 6, 8 on or after Day 2 of therapy (i.e. during the fourth dose) | 
| Avibactam effluent concentrations | mg/L | At hours post dose: 0, 2, 3, 4, 6, 8 on or after Day 2 of therapy (i.e. during the fourth dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | mg/L | At hours post dose: 0, 2, 3, 4, 6, 8 on or after Day 2 of therapy (i.e. during the fourth dose) | 
| Number of participants with adverse effects as a measure of safety | Measure of safety | Days 1-30 | 
| Minimum plasma concentration (Cmin) | mg/L | At hours post dose: 0, 2, 3, 4, 6, 8 on or after Day 2 of therapy (i.e. during the fourth dose) | 
| Half-life (t1/2) | hours | 8-hours | 
| Clearance (Cl) | L/hr | 8-hours | 
| AUC 0 to 8 hours | mg*hr/L | 8-hours | 
| Sieving Coefficient | SC | 8-hours |