Adequacy of Perioperative Cefazolin for Surgery Antibiotic Prophylaxis in Obese Patients

The population continues to increase in weight. Currently there are no guidelines in the dosing of cefazolin for the obese population. Standard dosing of cefazolin 2 grams for patients <120 kg and 3 grams for patients >120 kg is used as the dose for surgical prophylaxis. This makes no provisions for weight based dosing. There has been some recent data which states this might not be enough for the obese patients. The primary objective of this study is to determine if weight based dosing (30 mg/kg) of cefazolin as surgical prophylaxis for patients undergoing elective gastric bypass/laparoscopic Roux-en-y gastric bypass provides appropriate serum concentrations for a larger percentage of time than the current method of giving the standard 2 or 3 gram doses of cefazolin peri-operatively. The concentration of cefazolin in tissue will also be measured to help assess this question.

Study Overview

• Status: Withdrawn
• Conditions: Obesity
• Intervention / Treatment: Drug: Standard Dose Group; Drug: Weight Based Group

Detailed Description

The hypothesis of this study is that customary doses of antibiotics, when administered for perioperative surgical prophylaxis, are insufficient to achieve adequate antibiotic concentrations in blood and tissues of morbidly obese patients (defined as a BMI greater than 40 kg/m2) and that these patients are therefore placed at high risk of surgical wound infections and poor clinical outcomes. Cefazolin is a first-generation cephalosporin commonly used for perioperative surgical prophylaxis in colorectal, abdominal, bariatric, gynecologic and obstetric, or orthopedic total joint arthroplasty surgical procedures. Previous cefazolin pharmacokinetic (PK) analysis in obese patients led to conflicting results and recommendations. It is not clearly know to what extent the pharmacokinetics of cefazolin in morbidly obese patients differ from those of non-obese patients. Specific dosing guidelines are then lacking. The main objective of this study is to assess the pharmacokinetics of cefazolin in morbidly obese after administrations of a standard recommended 2-3 g dose or a weight-base 30-mg/kg dose

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. BMI greater than 40
2. No known history of allergy to cephalosporins
3. Scheduled for elective gastric bypass or laparoscopic Roux-en-y gastric bypass procedures
4. Able to read and understand English

Exclusion Criteria:

1. Patients <18 years of age or >89 Years of age
2. Pregnant women, prisoners and decisionally challenged subjects will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Standard dose group (2 g intravenous (IV) cefazolin dose for patients <120 kg, and 3 g IV cefazolin for patients >120 kg)	Drug: Standard Dose Group; The standard dose of Cefazolin will be administered intravenously.
Experimental: Treatment group; Weight-based dose group (30 mg/kg cefazolin IV)	Drug: Weight Based Group; The weight-based dose group will receive 30 mg/kg cefazolin dose intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the Pharmacokinetics of Cefazolin in the Morbidly Obese	Since the goal of perioperative antimicrobial prophylaxis is to achieve free (unbound) serum and tissue drug levels that exceed the MIC for likely pathogens across the duration of the surgical procedure, and since redosing of cefazolin is recommended every 3-4 hours, PK/PD performance of cefazolin over that time frame will be analyzed. For the purposes of this study, pharmacodynamic targets are defined as fT>MIC (time during which free drug concentrations exceed pathogen MICs) of 100% over periods of up to 4 hours in duration. The PK/PD probability of target attainment (PTA) for pharmacodynamic goals and the cumulative fraction of response (CFR) for both cefazolin regimens will be compared. A PTA of ≥90% and a CFR of ≥ 90% for a dosage regimen (i.e., predicted to meet pharmacodynamic targets in ≥ 90% of the total bacterial population across the full range of MICs) are considered optimum.	Before cefazolin admin., then at 10, 30, 60, 120, 180 minutes after injection and at wound closure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of surgical site infection	The incidence of surgical site infection will be monitored and compared.	Within 1 month postoperatively
Hospital length of stay	The length of time the subject is hospitalized will be monitored and compared.	Hospital discharge
Hospital readmission	Hospital readmission within 1 month postoperatively.	Witihn 1 month after hospital discharge
Incidence of adverse outcomes	Adverse outcomes in these patients will be monitored and compared.	Within 1 month postoperatively

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Pierre Moine, M.D., University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2017
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: February 28, 2013
• First Submitted That Met QC Criteria: June 21, 2013
• First Posted (Estimate): June 26, 2013

Study Record Updates

• Last Update Posted (Actual): December 6, 2017
• Last Update Submitted That Met QC Criteria: December 4, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Morbidly Obese; Perioperative antibiotic prophylaxis
• Other Study ID Numbers: 12-1653

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No