Effect of Vancomycin After Catheter Replacement (VanCat)

Effect of Single-dose Vancomycin After Catheter Replacement for Suspected Central Line-associated Bloodstream Infection (CLABSI) on Resolution of Infection in Critically Ill Patients: A Single Center Randomized Open Label Controlled Trial

Randomized controlled trial of the effect of a single-dose intravenous Vancomycin after catheter replacement for suspected central line-associated bloodstream infection on resolution of infection in critically ill patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Central Line-associated Bloodstream Infection (CLABSI); Catheter-related Bloodstream Infection
• Intervention / Treatment: Drug: Vancomycin

Detailed Description

Patients on the local intensive care unit with suspicion of central line-associated bloodstream infection will be randomized to standard of care consisting of catheter replacement and blood and catheter tip cultures and to standard of care plus a single-dose vancomycin. The effect of the intervention on resolution of humoral inflammation and negativity of blood cultures will be assessed after 48 and 96 hours.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Suspected central line-associated bloodstram infection defined as:

• Catheterization with a non-tunneled CVC and
• Clinical signs of local catheter infection or any increase in humoral inflammatory markers (PCT, CRP, WBC) or elevated body temperature ≥ 38.3°C not otherwise explained.

Baseline CRP at screening ≥ 100 mg/L

Exclusion Criteria:

• known positive blood cultures at the time of randomization
• High risk situation warranting immediate empiric antibiotic therapy:
• endovascular implant (prosthetic valve, pacemaker, vascular graft)
• high-risk for endocarditis warranting endocarditis-prophylaxis
• Septic shock
• Catheter replacement not feasible or no further indication for central venous catheterization
• Known hypersensitivity to vancomycin or any component of the formulation.
• Administration of Vancomycin, Teicoplanin, Daptomycin or Linezolid <48 hours before enrolment.
• Enrolment in another clinical study
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Standard of care (SOC) + single-dose intravenous vancomycin 15mg/kg	Drug: Vancomycin; The investigational drug vancomycin is administered intravenously through a newly inserted peripheral or central venous catheter directly after removal of the 'old' catheters. The investigational drug is administered with a volume of 500ml normal saline (NaCl 0.9%) with a rate of maximal 1g per hour.
No Intervention: Control; Standard of care (SOC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of infection	Composite endpoint of absolute reduction of C-reactive protein and negativity of blood culture results at 48 and 96 hours (combinated with augmented binary method)	96 hours after catheter replacement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negativity of blood culture results	Negativity of blood culture results after 48 hours, 96 hours and both	48 hours and 96 hours after catheter replacement
Reduction of C-reactive protein	Absolute reduction of C-reactive protein (mg/dl) in plasma	48 hours and 96 hours after catheter replacement
Reduction of Procalcitonin	Absolute reduction of Procalcitonin (mcg/L) in plasma	48 hours and 96 hours after catheter replacement
Reduction of IL-6	Absolute reduction of IL-6 (ng/L) in plasma	48 hours and 96 hours after catheter replacement
Reduction of white blood cell count	Absolute reduction of white blood cell count (G/L)	48 hours and 96 hours after catheter replacement
28-day survival	Survival after a follow-up of 28 days or until hospital discharge	28 days
ICU-free days at day 28	Cumulative days not admitted to the intensive care unit in patients alive at day 28	28 days
Vasopressor-free days at day 28	Cumulative days of no vasopressor therapy in patients alive at day 28	28 days
Invasive mechanical ventilation-free days at day 28	Cumulative days of no invasive mechanical ventilation in patients alive at day 28	28 days
Antibiotic-free days at day 28	Cumulative days of no antibiotic therapy in patients alive at day 28	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of central line-associated bloodstream infections	Definition according to the National Healthcare Safety Network (NHSN - CDC) Patient Safety Component Manual 2021	from blood cultures drawn before replacement and at 48 and 96 hours
Blood culture	positivity of blood cultures	from blood cultures drawn before replacement and at 48 and 96 hours
Vancomycin level in plasma	Vancomycin level (mg/L) in plasma after 24 hours	24 hours after administration
Incidence of acute kidney injury	Incidence of new or worsening acute kidney injury according to the definition and classification of the KDIGO 2012 guidelines	28 days
Hypersensitivity reaction to Vancomycin	Hypersensitivity reaction in the following 6 hours after vancomycin administration/catether replacement. Hypersensitivity reaction is defined as any new of the following symptoms: flushing, erythema, pruritus, pains or muscle spasms in the back or chest, dyspnea or hypotension.	6 hours after catheter replacement

Collaborators and Investigators

• Sponsor: University of Zurich

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Vancomycin; Critical Care; Bloodstream Infection; Central Line-associated Bloodstream Infection; Catheter-related Bloodstream Infection
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Infections; Communicable Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: SD02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No