Cystatin-C C-guided Vancomycin Dosing in Critically Ill Patients: A Quality Improvement Project

Phase 1

Completed

• Conditions: Methicillin-resistant Staphylococcus Aureus; Critical Illness; Sepsis
• Interventions: Drug: Vancomycin; Other: Cystatin C dosing algorithm; Other: Creatine clearance dosing algorithm

• Registration Number: NCT02945241
• Lead Sponsor: Mayo Clinic

Brief Summary

Determine if a cystatin C-inclusive vancomycin dosing algorithm improved target trough achievement compared to creatinine clearance-guided vancomycin therapy in critically ill patients.

Detailed Description

This is a prospective, quality improvement study that evaluated critically ill patients initiated on intravenous vancomycin. Between January 2012 through October 2013, vancomycin was dosed at 15-20mg/kg at an interval guided by creatinine clearance using the Cockcroft Gault equation (control arm). Steady state trough concentrations were assessed prior to the 4th dose of a consistent regimen and compared to the individualized target trough range (10-15mg/L or 15-20mg/L) appropriate for the suspected or documented source of infection. Given low overall trough achievement observed with standard care, a quality improvement project was undertaken. After approval by local clinical practice committees with representation from the Division of Infectious Diseases, Pharmacy and Critical Care, a quality improvement project was undertaken to implement a new vancomycin dosing nomogram with dosing intervals based on the Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) creatinine-cystatin GFR equation, expressed in mL/min. After structured education was provided, the dosing algorithm was rolled out from December 2013 through May 2015 (intervention arm). Steady state target vancomycin trough achievement was compared between study arms with and without adjustment for potential confounders.

Study Timeline

• Study Start: 2014-04
• Primary Completion: 2015-06
• Study Completion: 2016-03
• Study First Submitted: 2016-10-24
• Study First Submitted QC: 2016-10-24
• Study First Posted: 2016-10-26
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-06
• Last Update Posted: 2023-10-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 399

Inclusion Criteria

• Hospitalized in one of three intensive care units at Mayo Clinic in Rochester, Minnesota
• Suspected or documented gram-positive infection
• Prescribed IV vancomycin at a consistent dose and scheduled with 8, 12, or 24 hour Vancomycin dosing interval

Exclusion Criteria

• Vulnerable population
• Received greater than 1 dose of Vancomycin in the 96 hours before ICU admission
• Baseline glomerular filtration rate (GFR) of less than 20 milliliters/minute
• Undergoing renal replacement therapy
• Body mass index > 40kg/m2
• Weight < 40kg

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cystatin C-guided vancomycin dosing algorithm	Cystatin C dosing algorithm	Cystatin C is an endogenous cysteine proteinase inhibitor produced by all nucleated cells and a biomarker used routinely to estimate glomerular filtration rate either alone or in combination with creatinine. This new dosing algorithm includes patient weight, individualized goal trough concentration, and glomerular filtration rate (expressed with the CKD-EPI creatinine-cystatin C equation in mL/min) to determine dose and frequency.
Creatinine clearance guided vancomycin dosing	Creatine clearance dosing algorithm	Historical controls for the quality improvement project had doses based on weight and interval established with the creatinine clearance using the Cockcroft-Gault equation.
Cystatin C-guided vancomycin dosing algorithm	Vancomycin	Cystatin C is an endogenous cysteine proteinase inhibitor produced by all nucleated cells and a biomarker used routinely to estimate glomerular filtration rate either alone or in combination with creatinine. This new dosing algorithm includes patient weight, individualized goal trough concentration, and glomerular filtration rate (expressed with the CKD-EPI creatinine-cystatin C equation in mL/min) to determine dose and frequency.
Creatinine clearance guided vancomycin dosing	Vancomycin	Historical controls for the quality improvement project had doses based on weight and interval established with the creatinine clearance using the Cockcroft-Gault equation.

Primary Outcome Measures

Name	Time	Method
Vancomycin target trough achievement	Baseline	The percentage of initial steady state troughs within the target range.

Secondary Outcome Measures

Name	Time	Method
Length of stay (hospital and ICU)	Baseline
Treatment failure	7-days	Treatment failure in patients with confirmed gram-positive infection after at least 48-hours of vancomycin therapy and within 7-days
Infection recurrence	28-days	New onset of infection within 28-days among patients with confirmed gram-positive infection
Acute kidney injury (AKI) and renal replacement therapy	7-days	New onset AKI, defined as KDIGO stage II or greater AKI, within 48-hours of and within 7-days of vancomycin initiation