Antimicrobial Pharmacokinetics in Critically Ill Adults During Sustained Low Efficiency Dialysis (SLED)

NCT02242006 | Completed

• 1 other identifier: 20140429
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Severe acute kidney injury (AKI) is a common complication of critical illness affecting almost half of all patients with septic shock. Extracorporeal renal replacement therapy is a cornerstone in the management of AKI in these patients. Options for renal replacement therapy include continuous renal replacement (CRRT) therapy, intermittent dialysis (IHD) or a hybrid form of the two called sustained low efficiency dialysis (SLED). Globally there is a push to switch from traditional CRRT to SLED. Although there are resource and financial comparative benefits to SLED there is almost no literature describing how to dose antimicrobials (or other drugs for that matter). It appears that drug clearance on SLED may be more efficient than CRRT but not as efficient as IHD making extrapolation from these bodies of literature inappropriate for SLED. The investigators are proposing to conduct the population pharmacokinetic studies for the three most commonly used antimicrobials in critically ill patients receiving SLED therapy (piperacillin-tazobactam, meropenem and vancomycin). Population pharmacokinetic modeling of these drugs will provide estimates and sources of variability around pharmacokinetic parameters that will subsequently be used for Monte Carlo simulation to determine the most appropriate dosing regimens to achieve therapeutic targets while minimizing the risk of toxicity.

Conditions

Critical Illness; Kidney Injury; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• drug clearance

  Serial serum samples will be obtained after drug administration and during SLED to determine drug clearance during SLED.

  During the first run of SLED after study inclusion

• volume of distribution

  Serial serum samples will be obtained after drug administration and during SLED to determine drug volume of distribition during SLED.

  During the first run of SLED after study inclusion

Study Arms (3)

piperacillin/tazobactam

Serial serum sampling of patients receiving piperacillin/tazobactam and SLED simultaneously

Other: serial serum sampling for quantification of drug concentration

meropenem

Serial serum sampling of patients receiving meropenem and SLED simultaneously

Other: serial serum sampling for quantification of drug concentration

vancomycin

Serial serum sampling of patients receiving vancomycin and SLED simultaneously

Other: serial serum sampling for quantification of drug concentration

Interventions

serial serum sampling for quantification of drug concentration OTHER

meropenem; piperacillin/tazobactam; vancomycin

Eligibility Criteria

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

Study Population

critically ill adults admitted to an ICU

You may qualify if:

• Critically ill adults \[age ≥ 18\] admitted to one of two of the medical/surgical intensive care units (ICUs) of The Ottawa Hospital, who require SLED and are or will receive meropenem, piperacillin-tazobactam or vancomycin therapy at any dose.

You may not qualify if:

• Patients for whom participation via the informed consent process is denied.
• Critically ill patients with a hypermetabolic state due to \>25% coverage of body surface area burn, cystic fibrosis, spinal cord injury, bariatric patients (defined as \>150kg total body weight)
• Patient is pregnant as per a positive serum or urine βHCG qualitative assay
• Patient does not have a closed-system arterial or central venous catheter (to minimize blood wastage)
• Patients receiving concomitant drugs known to interact with the metabolism or clearance of the antimicrobial of interest according to Micromedex 2.0 (Truven Health Analytics Inc 2013)

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: September 16, 2014
• Study Start: October 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 29, 2021

Record last verified: 2014-09

Locations

CA (1)