Clinical trial NCT05253339: The Expected Advantage of Administering Prophylactic Antibiotics Using Target- Concentration Controlled Infusion
Official title: A Single-center Randomized Controlled Trial Comparing the Standard Method and Target-controlled Infusion as a Method of Administering Cefoxitin, Which is Used to Prevent Surgical Site Infections in Colorectal Surgical Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anti-bacterial Agents
Pharmacokinetics
General Surgery
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Seoul Business Agency
First posted: 2022-02-23
Enrollment: 2494
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: When administering cefoxitin, the standard administration method and the target concentration control injection method are randomly assigned 1:1.
Primary purpose: TREATMENT

Brief summary: Preoperative antimicrobial prophylaxis is a key element for the prevention of surgical site infection, the most common type of nosocomial infection in surgical patients. Prophylactic antibiotics are selected depending on the type of surgery, and first- or second-generation cephalosporins have been mainly used. Cefoxitin, a second-generation cephalosporin with anaerobic activity, has been used in various clinical settings as a prophylactic antibiotic for colorectal surgery. Cefoxitin is generally dissolved in normal saline and intravenously administered for a short time of 5-10 minutes before skin incision. However, there are several drawbacks to the current dosing strategy. First, the dose of cefazolin is determined by a "rule of thumb", and there is controversy over whether 1 g or 2 g is appropriate, with the opinion that 2 g being more appropriate prevailing. Second, the standard administration method unnecessarily induces a concentration higher than the concentration required to prevent surgical site infection. Third, significant covariates that can affect the maintenance of MIC during surgery are not considered. The target-concentration controlled infusion (TCI) method can be a viable alternative administration method for antibiotics. The TCI method enables individual customized administration according to the covariates (i.e., weight, creatinine clearance) included in the pharmacokinetic parameters; also, although with some variability, the drug can be administered while maintaining the target concentration. The aim of this study was to evaluate the effectiveness of administering cefoxitin in patients undergoing colorectal surgery with a syringe pump equipped with a target concentration control injection function

Detailed description: Parenteral antimicrobial prophylaxis before abdominal surgery for preventing surgical site infection (SSI) is a well-established clinical practice. Prophylactic antibiotics are selected depending on the type of surgery, and first- or second-generation cephalosporins have been mainly used. These antibiotics are generally dissolved in normal saline and intravenously administered for a short time of 5-10 min before skin incision. However, the conventional administration strategy has several problems. First, the dose of antibiotics does not take into account the patients' physical characteristics such as body weight, age, and renal function. Considering that the dosages of practically all drugs used in clinical fields are determined based on body weight, it may be necessary to improve the dosing strategy to reflect the patient's physical characteristics based on the effectiveness and safety of the antibiotic. Second, the plasma concentration of cephalosporin becomes excessively high at the end of the administration, which is more pronounced in patients with low body weight. The minimal inhibitory concentrations (MIC) for each antibiotic are well-characterized; however, a pilot simulation study showed that at the end of the administration, the plasma concentration of cefazolin was 20 times higher than its MIC. It is difficult to exclude the possibility that concentrations higher than necessary may cause harm to patients. Third, the bactericidal activity of an antibiotic is apparent when its free plasma concentration is maintained above the MIC. Using the conventional administration method, there is a period during the entire surgical period in which the concentration decreases below the MIC unless redosing is performed. Taken together, it is necessary to develop a method for administering a prophylactic antibiotic to overcome these problems.

The target-controlled infusion (TCI) is a method of administering a drug while maintaining a target concentration and has been used for more than 20 years for administering hypnotic agents and opioids during general anesthesia. Because the infusion rate is continuously recalculated by an infusion algorithm mounted on the TCI infusion pump to maintain the target concentration, the infusion rate is not fixed and changes over time. The patient's specific characteristics such as body weight and creatinine clearance can be included in the pharmacokinetic parameters so that even when administered for the same duration and the same target concentration, the actual dosage varies for each patient and allows for personalized administration. Thus, the population pharmacokinetic parameters of a drug are required to administer the drug by the TCI method.

The risk of SSI varies depending on the type of surgery, and colorectal surgery is regarded as having a high risk of SSI because of the possibility of wound contamination from bowel contents. Accordingly, the incidence of SSI has been reported to be 4-10% in colon surgery and 3-27% in rectal surgery. In the case of colorectal surgery, the optimal prophylactic antibiotic has not been unified into one agent. Cefoxitin, a second-generation cephalosporin with anaerobic activity, has been used in various clinical settings as a prophylactic antibiotic for colorectal surgery.

The aim of this study was to evaluate the effectiveness of administering cefoxitin in patients undergoing colorectal surgery with a syringe pump equipped with a target concentration control injection function

Eligibility criteria: Inclusion Criteria:

* over 20 years old
* Patients who are scheduled to undergo colon or rectal surgery
* Patients scheduled to receive cefoxitin as a prophylactic antibiotic

Exclusion Criteria:

* Known allergies, hypersensitivity, or intolerance to cefoxitin
* Patients with a history of receiving cefoxitin within 3 days of the scheduled surgery time
* Patients receiving therapeutic antibiotics
* eGFR \< 30 ml/min/1.73m2

Primary outcomes:
measure: The incidence of surgical site infections
timeFrame: Within 30 days after the operation
Secondary outcomes:
measure: Total dose of cefoxitin
timeFrame: on the day of surgery
Other outcomes:
measure: The incidence of acute kidney injury
timeFrame: Within 7 days after the operation
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa-Gu,
Study officials:
affiliation: Asan Medical Center
name: Byung-Moon Choi, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: