Study of Obese Patients Comparing Two Vancomycin Loading Dose Regimens

Study Overview
=================
Brief Summary
-----------------
Obesity alters the movement through the body of several antibiotics, including vancomycin. Based on literature to date, total body weight should be used to determine dosages and shorter dosing intervals may be needed. However, hospitals have different approaches to managing vancomycin in this patient population. The most common example is not exceeding a dose of 2,000mg of vancomycin at one time in these patients. However, some institutions including the Charleston Area Medical Center do not have a set maximum one time dose. To date, a study has not been done comparing two different dosing regimens in obese patients to determine if having a maximum dose cap is beneficial. This research study is attempting to add to the limited existing body of literature regarding vancomycin dosing in obese patients. The investigators hypothesize that optimizing the initial or loading vancomycin dose that obese patients receive will decrease the time to target concentrations. For this study, obese adult patients will be randomized to receive either 1) a loading dose of 20 mg/kg with a maximum dose up to 2,000mg OR 2) a loading dose of 20 mg/kg with a maximum dose of up to 4,000mg. The study's primary aim is to determine differences in the time needed to achieve target vancomycin concentrations and the occurrence of adverse events.

Official Title
-----------------
Single-Center Prospective Study of Obese Patients Comparing Two Vancomycin Loading Dose Regimens

Conditions
-----------------
Infection, Sepsis, Obesity

Intervention / Treatment
-----------------
* Drug: IV vancomycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ≥18 years of age who present to the Charleston Area Medical Center-Memorial Hospital Emergency Department Weight >100kg Infection requiring intravenous vancomycin and admission to Charleston Area Medical Center-Memorial Hospital Exclusion Criteria: Any patient <18 years of age Patients on dialysis or with unstable renal function (a change of >0.5 mg/dL in SCr concentration in patients with a SCr of <2 mg/dL or a 20% change in SCr in patients with a SCr of ≥2 mg/dL)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV Vancomycin loading dose- higher<br>IV Vancomycin loading dose: 20 mg/kg with a maximum dose of 4,000mg | Drug: IV vancomycin<br>* IV vancomycin for the treatment of infection. Following the vancomycin loading dose, vancomycin dosing will be at the discretion of the pharmacist and attending physician and will follow standard of care.<br>|
| Experimental: IV Vancomycin loading dose- lower<br>IV Vancomycin loading dose: 20 mg/kg with a maximum dose of 2,000mg | Drug: IV vancomycin<br>* IV vancomycin for the treatment of infection. Following the vancomycin loading dose, vancomycin dosing will be at the discretion of the pharmacist and attending physician and will follow standard of care.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to attain therapeutic vancomycin concentrations |  | < 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reported adverse events | Red Man's syndrome: pruritus and erythematous rash involving the face, neck, and upper torso. Nephrotoxicity: increase in serum creatinine (SCr) by 0.5 mg/dL or 50% from baseline on two consecutive measurements. | 48 hours post initial vancomycin dose | 
| Examine the pharmacokinetic parameter of elimination rate constant (ke) following the loading vancomycin dose |  | 12 hours | 
| Examine the pharmacokinetic parameter of volume of distribution (Vd) following the loading vancomycin dose |  | 12 hours | 
| Intensive care unit length of stay |  | 30 days | 
| Hospital length of stay |  | 30 days | 
| In-hospital mortality |  | 30 days |