EUS-GBD vs Antibiotics for Patients at High Risk for Cholecystectomy

Sponsor

Chinese University of Hong Kong (Other)

Overall Status

Recruiting

CT.gov ID

NCT05893511

Collaborator

(none)

110

Enrollment

Location

Arms

32.2

Anticipated Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objectives Acute cholecystitis commonly occurs in elderly patients who are at high-risk for surgery. Whether upfront Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is advantageous over antibiotics first for mild acute cholecystitis is uncertain.

Hypothesis to be tested The aim is to compare EUS-GBD versus standard protocol (antibiotics first) as a definitive treatment, in very high-risk patients suffering from mild to moderate acute cholecystitis. We hypothesize that EUS-GBD can reduce the 1-year risk of recurrent acute cholecystitis.

Design and subjects This is an international randomised controlled study including consecutive patients suffering from acute cholecystitis that are very high-risk for cholecystectomy. The patients would be randomized to receive EUS-GBD or antibiotics first.

Interventions: EUS-GBD versus antibiotics

Main outcome measures:

The primary outcome is the rate of recurrent acute cholecystitis in 1 year. Other outcomes include technical and clinical success, post-procedural pain scores, analgesic requirements, adverse events, re-admissions, re-interventions, quality of life and cost analysis.

Data analysis All outcomes would be analysed according to the intention-to-treat principle. Kaplan-Meier method with the log-rank test will be used to compare differences in recurrent acute cholecystitis in 1 year. A health economic analysis will also be performed. Assuming a 17.1% difference in recurrent acute cholecystitis rates, a 2-sided P value of 0.05, a power of 80%, and a 10% dropout rate, 110 patients is required.

Expected results The findings of this study can help establish the role of EUS-GBD in management of high-risk patients suffering from acute cholecystitis over antibiotics alone and Percutaneous transhepatic gallbladder drainage.

Condition or Disease	Intervention/Treatment	Phase
Acute Cholecystitis	Procedure: Endoscopic ultrasound-guided gallbladder drainage Drug: Antibiotics first	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Upfront Endoscopic Ultrasound-guided Gallbladder Drainage (EUS-GBD) Versus Standard Protocol (Antibiotics First) for Mild to Moderate Acute Cholecystitis in Patients Who Are Very-high-risk for Cholecystectomy: A Randomized-controlled Trial.

Actual Study Start Date :

Apr 26, 2023

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Antibiotics first group Antibiotics first equals to intravenous antibiotics 2nd generation cephalosporin or equivalent). Antibiotics would first be given parenterally and then switched to oral form when patient can tolerate diet or when sepsis subside. It will be continued for at least a total of 7 days.	Drug: Antibiotics first Patients randomized to antibiotics first would be given intravenous antibiotics 2nd generation cephalosporin or equivalent). Antibiotics would first be given parenterally and then switched to oral form when patient can tolerate diet or when sepsis subside. It will be continued for at least a total of 7 days.
Active Comparator: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) Prior to the procedure, the patients would be kept fasted for 6 hours and antibiotics would be commenced (2nd generation cephalosporin or equivalent). Antibiotics would be continued for up to one week after the procedure.EUS-GBD would be performed by either the conventional or direct method.	Procedure: Endoscopic ultrasound-guided gallbladder drainage Prior to the procedure, the patients would be kept fasted for 6 hours and antibiotics would be commenced (2nd generation cephalosporin or equivalent). EUS-GBD would be performed by either the conventional or direct method. A 10mm stent system would be used if the largest gallstone is smaller than 10mm in size and a 16mm stent is used if the largest gallstone is larger than 10mm. The distal flange of the stent would be deployed under EUS guidance, followed by deployment of the proximal flange under endoscopic guidance. Once deployed, the gallbladder is completely emptied by suction and irrigation until the effluent through the stent is clean. The need of inserting an additional double pigtail plastic stent through the LAMS would be decided by the endosonographer. A course of antibiotics will be continued for 7 days after the procedure .

Arm

Intervention/Treatment

Active Comparator: Antibiotics first group

Antibiotics first equals to intravenous antibiotics 2nd generation cephalosporin or equivalent). Antibiotics would first be given parenterally and then switched to oral form when patient can tolerate diet or when sepsis subside. It will be continued for at least a total of 7 days.

Drug: Antibiotics first

Patients randomized to antibiotics first would be given intravenous antibiotics 2nd generation cephalosporin or equivalent). Antibiotics would first be given parenterally and then switched to oral form when patient can tolerate diet or when sepsis subside. It will be continued for at least a total of 7 days.

Active Comparator: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD)

Prior to the procedure, the patients would be kept fasted for 6 hours and antibiotics would be commenced (2nd generation cephalosporin or equivalent). Antibiotics would be continued for up to one week after the procedure.EUS-GBD would be performed by either the conventional or direct method.

Procedure: Endoscopic ultrasound-guided gallbladder drainage

Prior to the procedure, the patients would be kept fasted for 6 hours and antibiotics would be commenced (2nd generation cephalosporin or equivalent). EUS-GBD would be performed by either the conventional or direct method. A 10mm stent system would be used if the largest gallstone is smaller than 10mm in size and a 16mm stent is used if the largest gallstone is larger than 10mm. The distal flange of the stent would be deployed under EUS guidance, followed by deployment of the proximal flange under endoscopic guidance. Once deployed, the gallbladder is completely emptied by suction and irrigation until the effluent through the stent is clean. The need of inserting an additional double pigtail plastic stent through the LAMS would be decided by the endosonographer. A course of antibiotics will be continued for 7 days after the procedure .

Outcome Measures

Primary Outcome Measures

1-year recurrent acute cholecystitis rate [1-year]
recurrent acute cholecystitis rate in 1 year

Secondary Outcome Measures

Technical success [1-year]
Technical success is defined as the ability to access and drain the gallbladder by placement of a drainage tube or maintenance of good drainage.
Daily post-procedural pain scores for the first 7 days [7 days]
Pain assessment would be performed using the visual-analogue scale (1 to 100) on post-procedural days 1 to 7.
Type and dosage of analgesic required [an average of 7 days]
Type and the dosage of the analgesic required after procedure/administered of antibiotics would be recorded.
Adverse events [1-year]
Any adverse events occured in 1 year will be recorded
Total number of unplanned readmissions related to acute cholecystitis and reinterventions [1-year]
The total number and the reason of any unplanned readmissions related to acute cholecystitis and reinterventions in 1 year will be recorded.
Cost-effectiveness measurement [1-year]
All costs in the antibiotics first arm would be recorded: the cost of using antibiotics (dose, frequency, duration), the cost of Percutaneous Transhepatic Gallbladder Drainage (PT-GBD) and subsequent cholecystogram if any All costs in the EUS-GBD arm would be recorded: the cost of EUS-GBD procedure (including the procedure itself, anaesthesia, Lumen-apposing metal stents (LAMS), needle, guidewire), cost of managing complications if any All costs in both arms would be recorded: i. Index admission: the cost of investigations (blood test, imaging), medications, hospital stay ii. Unplanned readmissions: the cost of investigations, medications, reinterventions (cost of procedure and its equipment) iii. Cost of the follow-up clinic visits
Quality of life assessment [1-year]
EQ-5D on admission (before randomisation) and at every follow-up clinic visit
Clinical success [1-year]
Clinical success is defined as improvement in clinical symptoms and laboratory test (i.e. liver function test and complete blood count)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Consecutive patients aged ≥ 18 years old
Suffering from grade 1 or 2 acute calculous cholecystitis*
At very high-risk for early laparoscopic cholecystectomy due to poor premorbid conditions** or elderly patients suffering from acute cholecystitis but refused operations

Exclusion Criteria:

Patients with the following conditions are excluded from the study:

Pregnancy
Patients unwilling to undergo follow-up assessments
Patients with suspected gangrene or perforation of the gallbladder
Grade III acute cholecystitis33
Patients diagnosed with concomitant liver abscess or pancreatitis (defined as elevated serum amylase more than three times the upper limit of normal)
Altered anatomy of the upper gastrointestinal tract due to surgery of the esophagus, stomach and duodenum
Patients with liver cirrhosis, portal hypertension and/or gastric varices
Abnormal coagulation: International normalized ratio (INR) > 1.5 and/or platelets < 50.000/mm3
Previous drainage of the gallbladder
Patients suffering acute cholecystitis due to malignant cystic duct obstruction
Patients with life expectancy of less than 3 years