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

Impact of Cystatin-C C-guided Vancomycin Dosing Recommendation on Target Trough Achievement and Clinical Outcomes in Critically Ill Adults

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

Study Overview

• Status: Completed
• Conditions: Sepsis; Critical Illness; Methicillin-resistant Staphylococcus Aureus
• Intervention / Treatment: Drug: Vancomycin; Other: Cystatin C dosing algorithm; Other: Creatine clearance dosing algorithm

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 Type: Interventional
• Enrollment (Actual): 399
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cystatin C-guided vancomycin 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.	Drug: Vancomycin; Intravenous; Other Names: Vancocin; Other: Cystatin C dosing algorithm; Expressed in milliliters per minute
Other: Creatinine clearance guided vancomycin dosing; Historical controls for the quality improvement project had doses based on weight and interval established with the creatinine clearance using the Cockcroft-Gault equation.	Drug: Vancomycin; Intravenous; Other Names: Vancocin; Other: Creatine clearance dosing algorithm; Vancomycin dosing algorithm based on creatinine clearance, expressed in milliliters per minute; Other Names: Cockcroft-Gault

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vancomycin target trough achievement	The percentage of initial steady state troughs within the target range.	Baseline

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Erin Frazee, PharmD, RPh, Mayo Clinic

Publications and helpful links

General Publications

• Frazee EN, Rule AD, Herrmann SM, Kashani KB, Leung N, Virk A, Voskoboev N, Lieske JC. Serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients: a cohort study. Crit Care. 2014 May 29;18(3):R110. doi: 10.1186/cc13899.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: October 24, 2016
• First Submitted That Met QC Criteria: October 24, 2016
• First Posted (Estimated): October 26, 2016

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protease Inhibitors; Anti-Bacterial Agents; Cysteine Proteinase Inhibitors; Vancomycin; Cystatins
• Other Study ID Numbers: 14-002808

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO