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

Phase 3

Recruiting

• Conditions: Acute Cholecystitis
• Interventions: Drug: Antibiotics first; Procedure: Endoscopic ultrasound-guided gallbladder drainage

• Registration Number: NCT05893511
• Lead Sponsor: Chinese University of Hong Kong

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-27
• Study Start: 2023-04-26
• Status Verified: 2023-05
• Study First Submitted QC: 2023-05-29
• Last Update Submitted: 2023-05-29
• Study First Posted: 2023-06-08
• Last Update Posted: 2023-06-08
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antibiotics first group	Antibiotics first	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.
Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD)	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). Antibiotics would be continued for up to one week after the procedure.EUS-GBD would be performed by either the conventional or direct method.

Primary Outcome Measures

Name	Time	Method
1-year recurrent acute cholecystitis rate	1-year	recurrent acute cholecystitis rate in 1 year

Secondary Outcome Measures

Name	Time	Method
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	1. 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; 2. 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; 3. 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
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)
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.
Quality of life assessment	1-year	EQ-5D on admission (before randomisation) and at every follow-up clinic visit

Trial Locations

Locations (1)

The Chinese Universtiy of Hong Kong; 🇭🇰 Hong Kong, Hong Kong