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

Acute Cholecystitis Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05893511
• Other study ID #: 2022.518
• Status: Recruiting
• Phase: Phase 3
• Start date: April 26, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: Chinese University of Hong Kong
• Contact: Shannon Melissa Chan
• Phone: 35052627
• Email: shannonchan[@]surgery.cuhk.edu.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Consecutive patients aged = 18 years old

2. Suffering from grade 1 or 2 acute calculous cholecystitis*

3. 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

Related Conditions & MeSH terms

• Acute Cholecystitis
• Cholecystitis
• Cholecystitis, Acute

Intervention

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 .

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.

Locations

Country	Name	City	State
Hong Kong	The Chinese Universtiy of Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year recurrent acute cholecystitis rate	recurrent acute cholecystitis rate in 1 year	1-year
Secondary	Technical success	Technical success is defined as the ability to access and drain the gallbladder by placement of a drainage tube or maintenance of good drainage.	1-year
Secondary	Daily post-procedural pain scores for the first 7 days	Pain assessment would be performed using the visual-analogue scale (1 to 100) on post-procedural days 1 to 7.	7 days
Secondary	Type and dosage of analgesic required	Type and the dosage of the analgesic required after procedure/administered of antibiotics would be recorded.	an average of 7 days
Secondary	Adverse events	Any adverse events occured in 1 year will be recorded	1-year
Secondary	Total number of unplanned readmissions related to acute cholecystitis and reinterventions	The total number and the reason of any unplanned readmissions related to acute cholecystitis and reinterventions in 1 year will be recorded.	1-year
Secondary	Cost-effectiveness measurement	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	1-year
Secondary	Quality of life assessment	EQ-5D on admission (before randomisation) and at every follow-up clinic visit	1-year
Secondary	Clinical success	Clinical success is defined as improvement in clinical symptoms and laboratory test (i.e. liver function test and complete blood count)	1-year