Clinical trial NCT01786161: Prospective Evaluation of a Vancomycin Nomogram With a Continuous Infusion of Vancomycin for Surgical ICU Patients
Official title: Prospective Evaluation of a Vancomycin Nomogram With a Continuous Infusion of Vancomycin for Surgical ICU Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: MRSA - Methicillin Resistant Staphylococcus Aureus Infection
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2013-02-07
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Vancomycin is an essential antimicrobial which is frequently used in the ICU for suspected methicillin-resistant Staphylococcus aureus (MRSA) infection. Therefore, it is vital to optimize the dosing of vancomycin for this critically ill population. The most efficacious method of administering vancomycin is debated in the literature. Since vancomycin is associated with slow bactericidal activity, it is important to closely monitor serum concentrations so as to achieve early target serum concentration, particularly when treating aggressive S. aureus infections. One study has shown that vancomycin infused continuously may enable faster and more consistent achievement of a therapeutic serum concentration when compared to intermittent infusion. A faster achievement in the goal serum vancomycin concentration would be a protective factor for intensive care unit mortality in patients with MRSA infection.

Currently in the surgical ICU (SICU) of our institute, vancomycin is administered based on a vancomycin dosing nomogram. Less than fifty percent of the ICU patients following this nomogram achieved target vancomycin concentration of 15 after 24 hours. To better achieve target vancomycin concentration in 24 hours, we developed a new vancomycin dosing nomogram with a continuous infusion. The aim is to determine which of the two dosing nomogram is more efficient and safer for SICU patients.

Detailed description: Early administration of effective antibiotics is the cornerstone of management in septic patients; however, altered pharmacokinetics in critically ill patients has lead to subtherapeutic antibiotic exposure with standard antibiotic dosing and administration. This is further evidenced by low therapeutic target achievement with our intermittent vancomycin dosing nomogram. Administering vancomycin by continuous infusions may lead to achieving a therapeutic concentration and AUC24 more quickly than the administration by intermittent infusions as well as provide a more consistent concentration throughout the dosing period. Therefore, a new vancomycin continuous infusion nomogram was developed to increase the achievement of a goal vancomycin concentration within 24 hours.

We hypothesized that vancomycin administered as continuous infusion would achieve the therapeutic target sooner and more consistently than when administered as an intermittent infusion in critically ill surgical patients. The aims of this study were to determine the dosing differences between continuous (CIV) and intermittent (IIV) dosing in critically ill surgical intensive care unit (SICU) patients with preserved renal function and whether calculated Cockcroft-Gault Creatinine Clearance (CG CrCL) or measured creatinine clearance (CrCL) is a better predictor of vancomycin clearance.

Eligibility criteria: Inclusion Criteria:

* Male and non-pregnant female \> 18 years of age admitted to Surgical ICUs with suspected infection
* Calculated creatinine clearance \> 60ml/min

Exclusion Criteria:

* Age \< 18 years
* Allergic to vancomycin
* Calculated creatinine clearance \< 60ml/min
* Pregnant
* Vancomycin administration more than 8 hour and less than 24 hour prior to study enrollment
* Anticipated vancomycin treatment less than 2 days for surgical prophylaxis

Primary outcomes:
measure: Number of Participants Who Achieved the Target Vancomycin Concentration
timeFrame: 24 hours
Secondary outcomes:
measure: Time Required to Reach the Therapeutic Levels
timeFrame: as long as participants are receiving Vancomycin (mean (SD) 9 (3.8) days for continuous, 8.4 (4.1) days for intermittent)
measure: Vancomycin Concentration at 24 Hours
timeFrame: 24 hours
Other outcomes:
Locations:
city: Boston
country: United States
facility: MGH
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Hsin Lin, PharmD
role: PRINCIPAL_INVESTIGATOR
References: