Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT04804215 |
| Other study ID # |
Liver-01 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 25, 2022 |
| Est. completion date |
December 30, 2024 |
Study information
| Verified date |
January 2023 |
| Source |
Seoul St. Mary's Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Liver transplant surgery has been used as a major treatment modality for end-stage liver
disease, hepatocellular carcinoma and acute liver failure due to innovations in surgical
treatment of donors and recipients over the past decade. However, despite these advances,
biliary tract complications are considered the technical "Achilles tendon" of liver
transplantation because of their high incidence, long-term interventions and potential risk
of transplant failure. The incidence of biliary tract complications after liver
transplantation is still a high incidence, with a prevalence of 10-50% despite increasing
technology and experience worldwide. Biliary tract complications are typically biliary tract
leakage and biliary stricture, which are the cause of post-transplant morbidity and
transplant loss. Most of the bile leakage occurs within 3 months after surgery, and the
incidence of these early complications reaches 10-20%. Biliary stricture is a late
complication that usually occurs within 5-8 months and can occur up to 1 year. The incidence
of biliary stricture currently reported is still occurring in 5-30% of large clinical
studies.
The use of external T-tubes to reduce biliary tract complications has been discussed for many
years, and many published studies show no difference in biliary tract complications
regardless of the use of T-tubes, as well as T-tube-related cholangitis and tube removal.
Showed a relationship with certain morbidity rates, such as bile leakage.
Insertion of a stent into the bile duct has the advantage of preventing biliary complications
while avoiding the side effects associated with the use of external T-tubes. We presented a
preliminary study of 100 patients and confirmed that intrabiliary stents reduced biliary
tract complications, and not using an intrabiliary stent was an independent risk factor for
biliary stenosis.
Therefore, in this study, the purpose of this study was to determine the effective and
rational use of intrabiliary stents through a randomized clinical trial according to the use
of intrabiliary stents during biliary reconstruction in patients with liver transplant
surgery. In addition, it is expected that clinical usefulness has not been announced until
now in Korea, since a double-blind prospective randomized controlled clinical trial was
conducted according to the presence or absence of an intrabiliary stent during biliary
reconstruction in liver transplantation.
Description:
Aim of study
1. Primary end-point To compare and evaluate the incidence of biliary tract complications
within 6 months after surgery according to the presence or absence of an intrabiliary
stent during biliary reconstruction in liver transplantation.
2. Second end-point Postoperative complications related to intrabiliary stent (cholangitis,
acute pancreatitis, intestinal perforation, bleeding, etc.), liver transplantation and
6-month survival rate, hospitalization period, re-hospitalization, non-biliary
complications, and liver through comparative analysis The purpose of this study is to
check the clinical effectiveness of the use of an intrabiliary stent during
transplantation.
Subject selection criteria, exclusion criteria, number of target subjects and their rationale
1. Selection criteria ① 19 years old or older ~ under 70 years old
- Patients eligible for liver transplantation
- Patients who have consented to written consent
2. Exclusion criteria
- When performing hepato-plant anastomosis due to anatomical/biliary tract disease ②
Patients who are not eligible for liver transplantation
3. Target number of people and basis for calculation Since this study was compared with the
control group, 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 1.33% in the group with antibiotics and 3.36% in the group
without antibiotics. The difference between the ratio between the two groups is 2.02%
larger in the test group than in the control group, and as a result of calculating the
study subjects by assuming the upper limit of the confidence interval between the two
groups as the non-inferiority margin of 5.4%, 72 subjects per each group were required,
10%. When calculating the dropout rate, 80 subjects per group, a total of 160 subjects,
are required.
Study design
1. Clinical trial design This clinical trial is an exploratory clinical trial evaluating
the safety and effectiveness of the use of intrabiliary stents during surgery in liver
disease requiring transplantation. A screening test is performed on subjects who
voluntarily agreed to participate in the trial in writing. On the day of surgery, after
determining whether the selection/exclusion criteria are met, appropriate subjects are
randomly assigned to the test group and the control group at a 1:1 ratio. In the control
group, during bile duct anastomosis, a stent is not inserted into the bile duct, and the
test group is inserted into the bile duct.
On the OP day and on the discharge day, adverse reaction investigations, laboratory
tests, and physical tests are conducted for safety and efficacy evaluation to evaluate
postoperative pain and hospital stay. At one week after discharge from the hospital,
adverse reactions, laboratory tests, and physical examinations are performed through an
outpatient visit to evaluate the occurrence of postoperative complications related to
infection, complications other than infection, and the need for additional procedures.
In addition, the degree of postoperative pain, re-hospitalization, complications other
than infection, and the need for additional procedures are evaluated and compared when
visiting the emergency room due to the occurrence of postoperative infection-related
complications within one month after discharge.
2. Target registration and randomization method Subjects who agreed to voluntarily
participate in the trial after hearing the explanation about this clinical trial will be
given a subject identification code in the order in which they signed the consent form
at the screening visit.In this clinical trial, the comparability of the treatment group
is maximized and the treatment group's Randomization is performed to ensure the
scientific validity of the clinical trial by not involving the subjectivity of the
investigator in the assignment.
Block randomization is performed to divide the patients who satisfy the
selection/exclusion criteria and agree to participate in the clinical trial into 2
groups and allocate them at a 1:1 ratio. For randomization, a statistical expert
independent from this clinical trial generates a random assignment number using SAS
ver.9.4 (SAS Institute Inc, NC, Cary, USA) or higher for Microsoft Windows and assigns
it sequentially.
3. Operation and storage of random allocation In this clinical trial, randomization is
operated by a third party, and the investigator receives subject consent from the
subject during the screening period, and records necessary matters and test findings to
determine the subject selection/exclusion criteria. At this time, the subjects will be
given screening numbers in order.
Finally, whether or not to participate in the clinical trial is determined by checking
the suitability of the subject's clinical trial. Subjects who are determined to
participate in the clinical trial are enrolled in the clinical trial and assigned a
randomization number through a randomization envelope according to the randomization
method to the test group or control group on the day of surgery, and based on the
randomization table operated by the investigator (surgeon). Groups are allocated
according to the subject assignment number.
4. Blind and unblind This clinical trial is a single-blind clinical trial. It should not be
known to which group the subjects are assigned according to the assignment number, and
the randomization table is kept by a third party, and the assigned envelope is managed
in a separate place. During the clinical trial period, if blindfolding is required
before the completion of the clinical trial due to a serious adverse reaction, the
research manager contacts the randomization staff to review and approve the reason for
the blindfolding, and then proceed with the blindfolding procedure.
Criteria for end of study and early termination
1. Criteria for cancellation and dropout In the case of the following occurrences, the
clinical trial may be canceled or eliminated.
① When the subject requests to stop the test
② When the investigator judges that it is difficult to continue the clinical trial due
to a serious adverse reaction
③ In case of violation of selection/exclusion criteria or serious violation of clinical
trial plan
④ If the subject's follow-up observation is unsuccessful
⑤ When other testers decide that the test should be stopped
2. Treatment at the time of cancellation and dropout If a subject is discontinued or
eliminated from the clinical trial, the investigator shall record the date of
discontinuation and dropout, the reason for the discontinuation and dropout, and the
treatment and progress at the time of discontinuation and dropout, along with all data
acquired until the time of discontinuation and dropout. Subjects with early
discontinuation in the clinical trial for any reason are not replaced.
Study method
1. Clinical trial intervention plan
- Test group: stent insertion into the bile duct. (silastic stent)
- Control: No stent insertion into the bile duct. Only subjects who have consented to
participate in the clinical trial and have been randomly assigned to meet the
criteria for selection/exclusion will perform the procedure.
2. Observation and inspection items
- Written consent and demographic survey, physical measurements, vital signs Before
entering the clinical trial, the investigator explains in detail the purpose and
contents of this clinical trial to the subject and obtains written consent. After
written consent, demographic information is investigated in the case record, and
the date of written consent, subject's initials, gender, date of birth, etc. are
recorded, and physical measurements (height, weight, BMI) and vital signs (systolic
blood pressure, diastolic blood pressure, pulse, body temperature) Also measure and
record. After each visit, physical measurements (weight, BMI) and vital signs
(systolic blood pressure, diastolic blood pressure, pulse, and body temperature)
are also measured and recorded.
- Investigation of medical history and drug administration history At the
screening visit, the interview and past medical records are reviewed, and the
subject's entire life history is investigated and recorded based on the
screening visit. In addition, after investigating and recording all drugs
taken from 30 days prior to the screening visit, and checking whether there is
a change in the condition of administration of the combination drug that was
investigated during the screening test at each visit thereafter, and whether
there is a new combination drug, Record it on the case record.
- Physical and laboratory tests Physical and laboratory tests (blood and
urine tests) are performed through screening visits and interviews at
that visit, and the test results and normality are recorded in the case
report.
④ ASA class According to the physical condition classification system
established by the American Society of Anesthesiology, an evaluation is
made between 1 and 6 points according to the physical condition of the
patient undergoing surgery and anesthesia and recorded in the case
report.
⑤ Imaging examination investigation Imaging tests should be collected if
there are any results.
⑥ Surgery, hospitalization information investigation The following items
are investigated for information on surgery and hospitalization.
• Anesthesia time from start to finish
• Operation time from abdominal incision to skin suture
• Surgery time required for resection
- Bleeding and intraoperative blood transfusions:
-Measured in cc, taking into account the amount of blood inhaled
during surgery and the weight of tape and gauze.
- The amount of red blood cells and whole blood administered
during surgery is measured in cc.
- After surgery, the investigator evaluates the patient's recovery
status (when the gas is released) once a day.
- Evaluation items for patient recovery status: Record the progression
of meals once a day every day, and if discharge is not made, the
record of the progression of meals and postoperative complications
on the discharge date is finally evaluated.
- Investigation of complications related to infection
Infection-related complications are divided into surgical site
infection and wound infection, and other complications are
investigated as non-infection-related complications. Symptoms
such as fever are not collected as complications, but the cause
is investigated and classified as complications. In addition,
if additional procedures are needed due to the occurrence of
related complications, the information should be collected.
3. Inspection items for each visit
- Visit 1 (Screening, -28D ~ pre OP) • written consent
- Determination of conformity to the selection/exclusion criteria
- Demographic information and medical history survey
- Physical examination
- Physical measurement/Vital signs
- Pre-drug investigation
- ASA class
- Abdominal ultrasound
- Laboratory tests
- Imaging examination investigation
- Evaluation of pain level (VAS score)
- Visit 2 (Baseline, OP day, surgery day)
- Determination of conformity to the selection/exclusion criteria
- Physical examination
- Physical measurement/Vital signs
- ASA class
- Surgery Information Survey
- Investigation of complications related to infection
- Random assignment
- Clinical trial intervention
- Visit 3 (post OP±1D, discharge date)
- Physical examination
- Physical measurement/Vital signs
- Concomitant drug investigation
- ASA class
- Laboratory tests
- Hospitalization information investigation
- Investigation of complications related to infection
④ Visit 4 (1W±1D)
- Physical examination
- Physical measurement/Vital signs
- Concomitant drug investigation
- ASA class
- Hospitalization information investigation
- Investigation of complications related to infection
⑤ Unscheduled visit (when visiting the emergency room) (OP+30D)
- Hospitalization information investigation
- Investigation of complications related to infection
- Adverse reaction evaluation
