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

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.

Overview

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.

Interventions

• 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 und
• 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.

Primary outcome measures

• 1-year recurrent acute cholecystitis rate [Time frame: 1-year]

Secondary outcome measures (9)

• Technical success [Time frame: 1-year]
• Daily post-procedural pain scores for the first 7 days [Time frame: 7 days]
• Type and dosage of analgesic required [Time frame: an average of 7 days]
• Adverse events [Time frame: 1-year]
• Total number of unplanned readmissions related to acute cholecystitis and reinterventions [Time frame: 1-year]
• Cost-effectiveness measurement [Time frame: 1-year]
• Quality of life assessment [Time frame: 1-year]
• Clinical success (clinical symptoms) [Time frame: 1-year]
• Clinical success (laboratory tests) [Time frame: 1-year]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Hong Kong · 1 center

• The Chinese Universtiy of Hong Kong — Hong Kong

Identifiers

NCT: NCT05893511 · 2022.518

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗