Effect of Vancomycin After Catheter Replacement

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Central Line-associated Bloodstream Infection (CLABSI), Catheter-related Bloodstream Infection

Intervention / Treatment
-----------------
* Drug: Vancomycin


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Standard of care (SOC) + single-dose intravenous vancomycin 15mg/kg | Drug: Vancomycin<br>* 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.<br>|
| No Intervention: Control<br>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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vancomycin, Central Line-associated Bloodstream Infection, Catheter-related Bloodstream Infection, Critical Care, Bloodstream Infection