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

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.

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.

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