CompletedPhase 2ACTRN12613000241730

Sampling Antibiotics in Renal Replacement Therapy, A Multinational Prospective Pharmacokinetic Study.

Multi-national prospective pharmacokinetic study, improving antibiotic dosing in renal replacement therapy for the five most commonly prescribed antibiotics Piperacillin-Tazobactam, Meropenem, Vancomycin and Imipenem and Linezolid at selected sites.

Sponsor

Nartional Health and Medical research Council

Enrollment

450 participants

Start Date

Apr 29, 2014

Study Type

Interventional

Conditions

Acute Renal Failure Renal Replacement Therapy

Summary

Inadequate antibiotic therapy is a critical determinant of survival in patients admitted to an Intensive Care Unit (ICU) with overwhelming infection requiring renal replacement therapy (RRT). Guidelines for effective dosing are not available because RRT can be vastly different between ICUs, resulting in significantly different antibiotic pharmacokinetics. Developing an evidence-based antibiotic dosing guideline is of global significance and should be considered a priority to improving clinical outcomes for patients requiring RRT that have infections.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria6

Age 18 years or older
Acute kidney injury requiring renal replacement therapy (defined according to published RIFLE, AKIN or KDIGO criteria)
Clinical indication for IV Piperacillin-Tazobactam, Meropenem or Vancomycin
Expected to be on filter for at least 4 days
Presence of intra-arterial line for blood sampling if renal replacement therapy filter port sampling not possible
Informed consent from patient or patient’s authorized representative

Exclusion Criteria4

Imminent death/not expected to survive etc.
Major bleeding or Haemoglobin <70g/L or platelets <20 x103/mm3.
Regular dosing with any of the 5 study antibiotics for greater than 36 hours, within the 7 days prior to enrolment
Unable to obtain consent

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

One of these study drugs (Piperacillin-Tazobactam, Meropenem, Vancomycin, Imipenem and Lizezolid) will be chosen, administered and dosed as per standard administration guidelines respective to the hospital. Participants will complete a full course of intravenous study drug for approx 7 days or as required by the site doctor to treat the associated infection. Study samples will be taken once on a dosing interval on days 1-2 and then again during a dosing interval between days 3-6. Serial samples of plasma, effluent and urine collections will be measured over either a 6, 8 or 12 hour study period to describe PK changes and potential resolution of infection as follows (assumes a 30-minute infusion for Meropenem or Piperacillin-Tazobactam and a 60-minute infusion for Vancomycin). Study samples will also be analysed to assess RRT clearance of drugs including sedatives and analgesics as well as micro nutrients (e.g. vitamin c , selenium).