Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04661371 |
| Other study ID # |
Seoul-S9 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 2, 2021 |
| Est. completion date |
December 30, 2021 |
Study information
| Verified date |
December 2020 |
| Source |
Seoul St. Mary's Hospital |
| Contact |
Tae ho Hong, MD. PhD |
| Phone |
+82-10-5206-5266 |
| Email |
gshth[@]catholic.ac.kr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In this study, the investigators compared the surgical outcomes according to the type of
antibiotics before surgery in patients who did not have evidence of systemic infection during
acute cholecystitis.
The primary purpose of the study was to determine the type of preoperative antibiotics in
patients who were scheduled for cholecystectomy, because of the mild (grade I) or moderate
(grade 2) acute inflammatory gallbladder disease without gallbladder perforation. The
investigators compared the incidence of postoperative complications according to the types of
preoperative antibiotics(the first-generation vs second-generation cephalosporin).
The secondary purpose of the study was to confirm the clinical efficacy of first-generation
cephalosporins following the use of empirical antibiotics. And the investigators compare with
postoperative pain, postoperative hospital stay, re-hospitalization, and need for additional
treatment. In addition, the investigators compare the postoperative complications, such as
atelectasis and postoperative ileus.
Description:
A. Background
B. Code name of clinical trial drug or medical device or generic name of main ingredient, raw
material drug (raw material in case of medical device) and its quantity, formulation (form /
structure / number in case of medical device), etc
1. Test drug : normal saline
2. control drug : Cefazolin inj., 1 g, Cefazolin sodium, white crystal, vial injection with
crystalline powder or lump
C. Target disease Acute cholecystitis without evidence of gallbladder perforation among
mild (Grade I) and severe (Grade II) classification of acute cholecystitis according to
Tokyo guidelines
D. Subject selection criteria, exclusion criteria, number of target subjects and their
rationale
1. 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
2. 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)
8. Drain tube is required during surgery (eg. if delayed biliary leakage was
concerned, hepatic duct injury was suspected or cystic duct ligation was
incomplete during operation.)
E. Calculation and basis of the number of target subjects In the previous studies,
infectious complications after laparoscopic surgery for acute inflammatory
gallbladder disease are reported as 2.5%, so it was designed as a non-inferiority
experiment between the two groups.After assuming power 80% and 2-sided confidence
level 95%, the dropout rate was 10%. Considering this, 90 people were assigned to
each group.
F. Random allocation schedule and operation Randomization was performed using block
randomization without stratification, and a block size of 2, 4 or 6 was applied to
complete the randomization table to maintain unpredictability, which was the basic
principle of randomization. .
G. Assignment bags with random assignment numbers and assigned groups were made of
opaque material so that they could be blinded and remain sealed until random
assignment was performed for each subject.
H. The person in charge of the clinical trial or the person in charge of the
clinical trial finally checked the exclusion criteria and, if it was a suitable
subject, a random number was assigned and stored in the allocation bag. Thereafter,
the management pharmacist receives the assignment bag with the assignment number,
releases the seal of the assignment bag, and prescribes antibiotics according to
the administration group assigned to the subject according to each random
assignment number. Afterwards, the managed pharmacist brought the antibiotics
according to the newly developed drug code for the clinical trial in accordance
with the [Medical Clinical Trial Management Standards (related to Article 30,
Paragraph 1)], and then administered to the patient. The management pharmacist
should record the release information (release date and releaser) immediately after
the release of the assignment bag which the random assignment enveloped, when it
had already been released once, it could not reassign the randomization code to
other subjects even if the subject withdraws consent.
I. Clinical trial method (administration / dosage, administration / use method,
administration / use period, combination therapy, etc.)
1. Research Design Prospective randomized controlled trial in two groups
2. Describe what treatment is performed for the experimental group / control
group A. Clinical trial flow
1. Before the patient's surgery, hematology, blood chemistry, blood coagulation,
urine, Chest X-ray, EKG, and Abdomen CT were performed in accordance with
current clinical practice guidelines.
2. Select the patient group that met the diagnostic criteria according to the
test results above.
3. Select a random patient group to determine the type of empirical antibiotic to
use before surgery
4. For each selected group, intravenous antibiotics (Cefazolin inj., 1 g,
Cefazolin sodium versus. normal saline) were used as before surgery.
- The clinical trial manager or the clinical trial manager finally checked the
criteria for selection exclusion and, if it was a suitable subject, a random
number was assigned and stored in the allocation bag. Thereafter, the
management pharmacist received the assignment bag with the assignment number,
released the seal of the assignment bag, and prescribed antibiotics according
to the administration group assigned to the subject according to each random
assignment number. Afterwards, the managed pharmacist brought the antibiotics
according to the newly developed drug code for the clinical trial in
accordance with the [Medical Clinical Trial Management Standards (related to
Article 30, Paragraph 1)], and then administered to the patient.
5. After surgery, both groups were discharged through the same recovery process
after surgery.
6. On the 1st day after surgery, hematology, blood chemistry, urine, blood
clotting, and chest x-rays were performed. (Inspection and treatment were
performed according to the current clinical pathway of gallbladder surgery)
7. If there are no specifics, a fluid diet was performed starting from lunch on
the first day after surgery.
8. If there were no specifics, patient would be discharged on the second day
after surgery.
9. Stability and effectiveness were monitored during hospitalization and after
discharge.
B. 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
ligated with a 10mm clip as well.
- If the cystic duct was unstablely ligated, ligation was performed through an
endoloop.
- 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.
C. Discharge Principle
1. When hematologically stable and vital signs were stable
2. When the patient's condition was stable by proceeding to the normal diet
J. characteristics of observational and clinical test
1) Medical history investigation Before entering the clinical trial, checked the
following items through interviews, chart and questions about the subject's
background (demographic information), medical history, etc., and recorded them in
the record.
(1) Background investigation: Subject's initials, date of birth, sex, feasibility
of pregnancy, pregnancy, lactation (2) medical history (3) History history: History
of other diseases 2) Physical examination, vital signs examination Investigators
checked whether the body organs were normal or abnormal through medical examination
and examination and any significant findings found during the examination should be
recorded in the physical examination column of the record sheet, and confirmed to
be suitable for participation in the study.
After surgery, the pain level was measured by questioning the patient himself using
the VAS score, and the amount of analgesics (injection drugs; tramadol and oral
drugs; ircodon) administered after surgery to the patient was recorded through
medication records.
3) Clinical examination
It was performed during the hospitalization after decision to perform
cholecystectomy. Blood sampling for the subjects was performed aseptically.
Investigators recorded the test results, determined whether they were normal or
abnormal, and record the opinions of researchers regarding abnormal values.
Clinical tests included :
1. Hematology tests: Hematocrit, Hemoglobin, MCV, MCH, MCHC, Platelet, WBC &
Differential count, ESR
2. Blood coagulation test: PT INR, aPTT, BT
3. Blood chemistry test: SGOT (AST), SGPT (ALT), alkaline phosphatase, γ-GTP,
bilirubin (total / direct), fasting plasma glucose, BUN, creatinine, sodium,
potassium, chloride, calcium, phosphorus, magnesium , total protein, albumin,
uric acid, CPK, LDH, free fatty acid, CRP, HbA1c, CRP
4. Urine test: Color, specific gravity, pH, Leucocytes, Nitrite, Protein,
Glucose, Ketone, Urobilinogen, Bilirubin, Microscopy (RBC, WBC) 4) Imaging
medical examination
1. Before surgery, chest X-ray and electrocardiography were performed to evaluate
whether surgery was possible.
2. Imaging studies such as CT, Sonogram, and MRCP were conducted. 5)
Postoperative hospital stay The day after surgery, hematology, blood
chemistry, urine, blood clotting, Chest x-ray.
6) Check for infection.
- Surgical site infection
1. Confirmation at every patient visit. Troca insertion site was defined as
superficial surgical site infection if there was redness, heat sensation and
abscess.
2. If there was fluid retention and abscess around the surgical site in the abdominal
cavity, it was defined as deep surgical site infection.
- Distant infection
- Respiratory, urinary system infections and bacteremia or lymphangitis 7) Check
for leakage of bile.
- Groups who had drainage catheter would be checked through the drainage
pattern. In the group without drainage catheter, after surgery, if there
is epigastric pain, indigestion, fever, and jaundice, a selective medical
imaging test (CT, sonogram, MRCP) was performed.
8) Surgery time, bleeding amount were described. 9) Postoperative
complications (things other than those described above) were described.
K. Predicted side effects and precautions
1. Side effects that might occur in the experimental group (the first-generation
cephalosporin use group)
- Wound infections and deep infections : Since antibiotics were used, the
possibility was very low.
- Side effects of antibiotics (allergic reaction)
2. Side effects that could be occurred in the control group (2nd generation
cephalosporin use group)
- Extension of the period of stay
- Increased hospitalization costs
- Increase of multi-drug resistant bacteria
- Side effects of antibiotics (allergic reaction) (In the event of side
effects, medical judgment was used to actively select a therapeutic
method.)
L. Stop or drop the test Dosing and testing should be discontinued if any of the
following occurs, and the reasons for discontinuation and findings should be
recorded.
1. After surgery, when a side effect that was life-threatening, the investigator
determined that it was necessary to stop
2. When the patient refused or withdrew consent after starting the test
3. If the patient was inadequate after starting the test
4. After the start of the test, if patient had received treatment that might
affect the course of treatment, such as other combination drugs and herbal
treatments, without the permission of the test manager
5. After the start of the test, it was judged that it was impossible to conduct
inspection or investigation due to the circumstances
6. After surgery, when surgery was required due to a disease of another organ not
related to gallbladder surgery.
M. Statistical analysis
1. Analysis of validity variables A. Analysis of primary efficacy variables.
- During the postoperative hospital stay, the incidence of wound infection
and deep infection rates in the group using the first-generation
cephalosporin and normal saline as an empirical antibiotic before surgery
was determined by the student's t-test or according to the satisfaction
of the normal distribution assumption. Test using wilcoxn's rank sum
test, and present the descriptive statistics (average, standard
deviation, median, minimum, and maximum). Also, the difference in the
incidence of infection between the two groups (test group-control group)
was presented as the mean and 95% confidence interval, and if it was less
than the non-inferiority limit of 13%, the group using the
first-generation cephalosporin antibiotics was the second-generation
cephalosporin. It was not inferior to the group using antibiotics. That
was, it would decide that it was not inferior.
B. Complications after surgery.
- Complications will be defined and analyzed through researchers'
experience and review of existing literature.
- Fever after surgery: Fever of 37.5 ° C or more that lasts at least
48 hours after surgery.
② Surgical site infection: In case of seroma, hematoma, or abscess
in the surgical incision.
③ Surgery wound wound: When the wound was opened and opened.
④ Coming, vomiting after surgery: If patient needed to use
antiemetic after 24 hours of surgery, or if patient had vomited even
once.
⑤ Sustained shoulder pain after surgery: If patient complained of a
stiff shoulder until the outpatient follow-up examination (one week
after discharge).
⑥ Bleeding after surgery: When the patient's vital signs change or
there was a decrease in Hb 2.0 or higher on the hemoglobin test the
day after surgery.
- Abscess in the abdominal cavity after surgery: When an abscess
in the abdominal cavity was confirmed by image examination
(ultrasound, CT, etc.) accompanied by fever and pain in the
physical examination.
- Persistent bowel obstruction: If the meal could not be
started even after 2 days of surgery.
2. Analysis of secondary efficacy variables 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, and the normality test was performed to test
with Student's t-test for normal distribution, and for the non-normal
distribution, Wilcoxon rank-sum test The difference between the two groups
would be tested. All statistical analysis would use SPSS version 21.0, and it
would be judged that it was statistically significant below the significance
level of 0.05.
3. Analysis target group
1. intention to treat analysis group Randomization would be performed only if the
selection criteria described above were met, and all randomized subjects would
be included in statistical analysis.
2. per protocol analysis group The Per protocol analysis group was defined as a
patient who had undergone randomization and had undergone chest imaging the
next day after surgery, and whose pain had been assessed.
4) How to deal with missing values This study was a prospective study, and it was
expected that there would be no missing values of the main or secondary endpoints
during the experiment. However, if a missing value occurred, the missing value was
substituted with the average value.
5) How to deal with compliance Since the intervention applied to this study was an
intervention performed during surgery while the patient had general anesthesia,
there would be no difference in treatment compliance. In addition, postoperative
thoracic imaging and pain assessment were also included in the clinical pathway for
laparoscopic cholecystectomy, so there was no difference in treatment compliance.
N. Safety evaluation of side effects and reporting method In the event of adverse
reactions and adverse reactions after surgery, trained the subject to report to the
researcher, checked and recorded the occurrence of adverse reactions at each visit,
symptoms, appearance time, duration, severity of adverse reactions, and causal
relationship with the test drug Record in the report. In the event of a serious
adverse event or unexpected problem, the responsible researcher should report it to
the clinical trial.
O. Compensation Protocol of victim Laparoscopic cholecystectomy was a safe
operation with a very low risk of surgery. Also, there are basically no additional
risks accompanying the study. Antibiotics were drugs that had been used before, so
there are no additional complications beyond the known complications. If patient
got injury or illness by participating in this study, medical treatment would be
provided. In order to receive medical treatment related to the clinical symptoms or
signs, investigators would make a quick diagnosis and receive treatment when needed
through consultation.
