Brief Title
Effectiveness of Empirical Antibiotic Use in Mild to Moderate Acute Inflammatory Gallbladder Disease
Official Title
Necessity and Effectiveness of Empirical Antibiotic Use in Mild to Moderate Acute Inflammatory Gallbladder Disease; a Multicenter, Double-blind, Randomized, Placebo-controlled Trial
Brief Summary
This clinical trial is an exploratory clinical trial that evaluates the necessity and
effectiveness of empirical antibiotic use in mild and moderate acute inflammatory gallbladder
diseases that require surgery, and the incidence of postoperative infection-related
complications is compared.
Detailed Description
Cholecystectomy is the standard treatment for acute cholecystitis, accompanied by pain and
fever due to acute inflammation in cholelithiasis patients. Empirical antibiotics are
generally used to treat inflammation and prevent exacerbation before and after surgery.
According to a previous study that confirmed the use of empirical antibiotics (JAMA.
2014;312(2):145-154. doi:10.1001/jama.2014.7586), the incidence of infectious complications
was 15% in the group that used empirical antibiotics, and 15% of those who did not use
empirical antibiotics The incidence of infectious complications in the group was 17%,
confirming that there was no significant difference between the two groups. Based on these
results, it was confirmed that the use of antibiotics after surgery was not clinically
effective in reducing postoperative complications of infection.
However, there is a lack of objective research and evidence on the efficacy of empirical
antibiotic use, and the use of antibiotics that have not been proven in practice may lead to
the extension of hospital stay, waste of medical resources, and an increase in medical
expenses. In addition, it can cause the occurrence of multidrug-resistant bacteria, which has
been revived due to many problems recently, so caution is required in its use.
If the same anti-inflammatory effect and postoperative results can be obtained only through
surgical treatment in mild and moderate acute inflammatory gallbladder disease, it is
expected that the indiscriminate use of antibiotics will be reduced, and side effects thereof
will be prevented. Therefore, this study intends to determine the effective and rational use
of antibiotics through randomized clinical trials according to empirical antibiotics in
laparoscopic surgery for patients with acute cholecystitis without evidence of systemic
infection. In addition, a multicenter, double-blind, prospective, randomized,
placebo-controlled clinical trial according to the use of empirical antibiotics has not been
conducted in Korea so far, and thus clinical usefulness is expected to be great.
study population
1. Inclusion criteria
- 19 years old or older - less than 70 years old
- Those with mild (grade I by Tokyo guidelines) and severe (Grade Ⅱ) acute
cholecystitis among the acute cholecystitis patient group
- Cholecystitis with adhesions with surrounding organs due to gallbladder wall
thickness of 4 mm or more or gallbladder inflammation
- Those who voluntarily sign the written consent form after hearing and understanding
the explanation of this clinical trial
2. Exclusion criteria
- Those who are scheduled for elective gallbladder surgery (chronic cholecystitis,
etc.)
- Gallbladder disease that is not an inflammatory disease (GB cancer, GB polyp)
- Pregnant or lactating women
- A person who performs surgery at the same time due to other organ diseases
- Those with immune suppression and bleeding tendency
- Those who underwent percutaneous biliary drainage (PTGBD) before surgery
- Those who require drainage tube installation during surgery
- Those who are hypersensitive to cephalosproline antibiotics
- Those who participated in other clinical trials within 3 months before screening
- Other investigators who are judged inappropriate to participate in this clinical
trial
3. Target number of subjects and calculation basis Since this study was a comparison with a
reference drug, the number of subjects was calculated using a non-inferiority test. To
calculate the number of study subjects, in the existing literature, the incidence of
surgical site infection was 15% in the group using antibiotics and 17% in the group not
using antibiotics. The difference value of the ratio between the two groups was 2%
larger in the test group than in the control group, and the study subjects were
calculated assuming 11%, the upper limit of the confidence interval between the two
groups, as the non-inferiority margin. As a result, 166 subjects in each group are
required, 10%. If the dropout rate is calculated, 185 per group, a total of 370
subjects, is required.
Study design
1. Design of clinical trials This clinical trial is an exploratory clinical trial
evaluating the safety and effectiveness of using empirical antibiotics in mild and
moderate acute inflammatory gallbladder disease requiring surgery. After determining
whether the selection/exclusion criteria are suitable on the day of surgery, only
suitable subjects are randomly assigned to the test group and control group in a 1:1
ratio. For the control group, the clinical investigational drug (Cefazolin 1g) was
administered through an intravenous injection within 1 hour before the surgical site
incision so that the concentration of antibiotics could be sufficiently maintained at
the time of incision at the surgical site and the test group was administered with
physiological saline without antibiotics do. Empirical antibiotics and saline are
administered repeatedly at 24-hour intervals from the first dose until the patient is
discharged.
On the day of operation (OP day) and discharge, adverse reaction investigations,
laboratory tests, and physical examinations for safety and efficacy evaluation are
performed to evaluate the postoperative pain level and hospitalization period. One week
after discharge, an outpatient visit is performed to evaluate adverse reactions,
laboratory tests, and physical examinations to evaluate postoperative pain, the
occurrence of postoperative infection-related complications, complications other than
infection, and the need for additional procedures. In addition, when visiting the
emergency room due to infection-related complications within a month after discharge,
evaluate and compare the degree of postoperative pain, readmission, complications other
than infection, and the need for additional procedures.
2. Method of subject registration and randomization Subjects who have listened to the
explanation of this clinical trial and agreed to voluntarily participate in the trial
will be given a subject identification code in the order in which they signed the
consent form at the screening visit. Randomization is performed to ensure the scientific
validity of clinical trials by ensuring that the subjectivity of the investigator is not
involved in the assignment.
Block randomization is performed to divide the patients into 2 groups and allocate them in a
1:1 ratio for patients who satisfy the selection/exclusion criteria and agree to participate
in the clinical trial. For randomization, a statistician independent of this clinical trial
generates a randomization number using SAS ver.9.4 for Microsoft Windows (SAS Institute Inc,
NC, Cary, USA) or higher and assigns them sequentially.
Method of operation
1. Surgery was started under general anesthesia
2. A trocar of 10 mm was placed on the navel, 5 mm under the blade, and 5 mm trocar was
placed on the right upper abdomen.
3. Pneumoperitoneum was performed using CO2 gas in the abdominal cavity.
- Double pressure through CO2 gas was maintained at 12mmHg / and 2L / min.
4. Dissection started from Calot's triangle, and the operation was performed by retrograde
cholecystectomy.
- The cystic duct was ligated with a 10mm clip, and the cystic artery was also
ligated with a 10mm clip.
- If the cystic duct was unstably ligated, ligation was performed through an end
loop.
- After ligation, the gallbladder was dissected from the liver.
5. Washed the surgical site.
6. The excised gallbladder was placed in a laparoscopic pocket and extracted through the
umbilicus.
7. The trocar was removed, the skin was sutured, and the operation was completed.
characteristics of observational and clinical test
- Hematology tests: Hematocrit, Hemoglobin, Platelet, WBC & Differential count
- Blood coagulation test: PT INR, aPTT, BT
- Blood chemistry test: SGOT (AST), SGPT (ALT), alkaline phosphatase, γ-GTP, bilirubin
(total / direct), fasting plasma glucose, BUN, creatinine, sodium, potassium, chloride,
total protein, albumin, uric acid, CPK, LDH, CRP
- Imaging medical examination
- Postoperative hospital stay
- Check for infection.
- Check for leakage of bile.
- Surgery time and bleeding amount were described.
- Postoperative complications
Statistical analysis In the case of categorical variables for the length of stay, surgical
time, and complication data obtained as secondary endpoints, n (%) was presented, and the
ratio difference between the two groups was tested using Chi-square or Fisher's exact test.
In addition, for continuous variables, the mean, standard deviation, median, minimum, and
maximum values were presented. The normality test was performed to test with Student's t-test
for normal distribution and the non-normal distribution Wilcoxon rank-sum test. The
difference between the two groups would be tested. All statistical analyses would use SPSS
version 21.0, and it would be judged that it was statistically significant below the
significance level of 0.05.
Study Type
Interventional
Primary Outcome
Number of Participants with Infectious Postoperative Complications
Secondary Outcome
Duration of hospitalization
Condition
Cholecystitis, Acute
Intervention
Laparoscopic cholecystectomy
Study Arms / Comparison Groups
The experimental group in acute cholecystitis
Description: inclusion criteria among patients with mild acute cholecystitis (grade I by Tokyo guidelines) or moderate acute cholecystitis without evidence of gallbladder perforation(grade II) cholecystitis with a thickness of 4 mm or more on gallbladder in preoperative imaging Gallbladder with surrounding organs due to gallbladder inflammation Patients over 19 years of age normal saline (Isotonic Sodium Chloride Injection Daihan(50mL/bag)) was used before surgery.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Procedure
Estimated Enrollment
370
Start Date
May 1, 2022
Completion Date
April 30, 2024
Primary Completion Date
April 30, 2023
Eligibility Criteria
Inclusion Criteria:
1. among patients with mild acute cholecystitis (grade I by Tokyo guidelines) or moderate
acute cholecystitis without evidence of gallbladder perforation(grade II)
2. cholecystitis with a thickness of 4 mm or more on gallbladder in preoperative imaging
3. Gallbladder with surrounding organs due to gallbladder inflammation
4. Patients over 19 years of age, under 70 years of age
Exclusion Criteria:
1. patients with elective gallbladder surgery (chronic cholecystitis)
2. gallbladder disease not inflammatory disease (GB cancer, GB polyp)
3. pregnant women, patients under 18 years of age, over 70 years of age
4. patients with simultaneous surgery due to other organ diseases
5. immunosuppressed patients; liver transplant patients, kidney transplant patients,
acquired immunodeficiency syndrome patients
6. patients with hemorrhagic tendency, or with hematologic diseases
7. Patients who underwent percutaneous cholecystectomy (PTGBD)
Gender
All
Ages
19 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Sung eun Park, MD, +82-10-5206-5266, [email protected]
Location Countries
Korea, Republic of
Location Countries
Korea, Republic of
Administrative Informations
NCT ID
NCT05339282
Organization ID
Seoul_S10
Responsible Party
Principal Investigator
Study Sponsor
Seoul St. Mary's Hospital
Study Sponsor
Sung eun Park, MD, Study Director, The Catholic University of Korea
Verification Date
May 2022