Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05253339 |
| Other study ID # |
2022-0180 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 4, 2022 |
| Est. completion date |
April 30, 2025 |
Study information
| Verified date |
March 2024 |
| Source |
Asan Medical Center |
| Contact |
Byung-Moon Choi, Ph.D. |
| Phone |
82230101704 |
| Email |
byungmoonchoi7[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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
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
