Surgical vs Endoscopic Treatments as ImmunoModulating Interventions in High-Risk Acute Calculous Cholecystitis (SETIMIHRACC)

Randomized controlled trial on high-risk patients with ACC. Consecutive patients with a diagnosis of ACC, if they meet the inclusion and exclusion criteria, will be randomized to receive Laparoscopic cholecystectomy (LC) or transmural ultrasound-guided gallbladder drainage (TUGD) with lumen-apposing self-expandable metal stents (LAMSs) within 10 days from onset of symptoms. Blood cultures will be performed at the time of admission, just before the procedure, 24 ± 3h after procedure, 72 ± 3h after procedure. Bile samples will be taken during the procedure for microbiological exam and culture. Blood samples will collected from all patients at the time of admission, just before the procedure, 24 ± 3h after procedure, 72 ± 3h after procedure.

The follow-up will be performed after 30 days and after 6 months from intervention with an outpatient medical examination.

Study Overview

• Status: Recruiting
• Conditions: High-risk Patients With Acute Calculous Cholecystitis (ACC)
• Intervention / Treatment: Procedure: Transmural ultrasound-guided gallbladder drainage; Procedure: Laparoscopic cholecystectomy

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luca Ansaloni, MD; Phone Number: +390382502530; Email: l.andaloni@smatteo.pv.it

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Recruiting
    • SC Chirurgia Generale 1 - Fondazione IRCCS Policlinico San Matteo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• have a diagnosis of ACC as defined by 2018 Tokyo Guidelines criteria
• be ≥ 18 years old
• have a POSSUM PS ≥ 25
• onset of symptoms <= 7 days before Emergency Department (ED) admission
• provide signed and dated informed consent form
• willing to comply with all study procedures and be available for the duration of the study
• have an Israelian Score (IS) (Table 3) for the risk of main bile duct stones <2 or an IS =2 and an EUS or a MRCP negative for main bile duct stones

Exclusion Criteria:

• Pregnancy
• Patients unwilling to undergo follow-up assessments
• Patients diagnosed with concomitant pancreatitis
• Acute cholecystitis not related to a gallstone etiology
• Onset of symptoms >7 days before ED admission
• Altered anatomy of the upper gastrointestinal tract due to surgery of the esophagus, stomach and duodenum
• Previous drainage of the gallbladder
• Biliary peritonitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transmural ultrasound-guided gallbladder drainage; Patients randomized to TUGD arm will receive endoscopic transmural ultrasound-guided gallbladder drainage with lumen-apposing self-expandable metal stents (LAMSs)	Procedure: Transmural ultrasound-guided gallbladder drainage; TUGD will be performed using the bi-flanged LAMSs mounted on an electrocautery-enhanced delivery system (Hot-AXIOS™) by an experienced endoscopist defined as > 10 LAMS positioning per year. The diameter and length of the stent and the modality of placing the stent (under complete EUS view or with endoscopic or fluoroscopic guidance) will be chosen at the discretion of the endoscopist performing the procedure
Active Comparator: Laparoscopic cholecystectomy; Patients randomized to control arm (LC) will receive laparoscopic cholecystectomy.	Procedure: Laparoscopic cholecystectomy; LC will be performed by the four-trocar technique with transection of the cystic duct and cystic artery after reaching the critical view of safety. ELC will be performed by a surgeon trained and experienced in laparoscopic surgery defined as > 5 laparoscopic procedures for ACC on a yearly basis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective of the study is to find if TUGD with LAMSs, compared to LC, has a lower inflammatory and immunologic impact on high-risk patients with ACC.	Difference between the plasma elastase concentration before surgery and on the third postoperative day	baseline, pre-surgery, day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
difference between the plasma concentration biochemical and immunological parameters	PTX (pentraxin-1, PCR), PTX2, PTX3, SAA (serum amyloid A) , PCT (procalcitonine), C3b, Pro-adrenomedullina, Cortisol, Hepcidin, TNFalpha, IL-1, IL-6, IL-8, IL-10 and IFNgamma, total WBC count, WBC subpopulation (neutrophils and total lymphocytes), T-helper lymphocytes (CD4), T-suppressor lymphocytes (CD8), natural killer lymphocytes (CD16 and CD56), pan B cell antigen (CD20), T-cell receptor gamma/delta, T reg, Th 17, human leukocyte antigen-DR (HLA-DR)	baseline, pre-surgery, day 1, day 3
30-day postoperative complication rate according to Clavien-Dindo	Rate of: biliary tree injury, hemorrhage, wound infection, deep infection (collections, abscesses), urinary tract infection, bowel perforation, biliary leakage, paralytic ileus, respiratory complication, cardiac complication, renal complication, cerebrovascular complication, thrombo-embolic complication, other	day 30
30-day postoperative biliary complication rate	Rate of biliary leakage and main biliary duct injury	day 30
30-day postoperative mortality rate	Mortality rate	day 30
Intraoperative complication rate	Rate of bleeding >500ml, Biliary tree injury, Bowel perforation, Major vascular injury, Anesthesia respiratory complications, Anesthesia cardiac complications, Other	day 0
Failure rate of performing the procedure	Rate of failure	day 0
Operative times	Procedure duration (measured from skin incision to skin closure for LC and from the introduction of the endoscope to its extraction for if TUGD with LAMSs) (minutes); Time of occupation of the operating room (minutes); Time from admission to the ED to the procedure (days); rate of patients who used the prescribed painkiller "to need"; average of daily administrations of painkillers prescribed "to need" in the first post-procedure day; rate of patients where postoperative pain management therapy had to be varied compared to protocol	through study completion, an average of 2 years
Postoperative length of stay (PO-LOS)	Postoperative length of stay (days)	through study completion, an average of 2 years
Total length of stay (T-LOS)	Total length of stay (days)	through study completion, an average of 2 years
Total readmission rate within 6 months	Readmission rate for all causes	6 Months after procedure
Readmission rate within 6 months due to Gallstones Relates Events (GRE)	Readmission rate due to biliary colic, acute cholecystitis, acute pancreatitis, obstructive jaundice and cholangitis	6 Months after procedure
Outcomes of blood and bile cultures (to define the infectious state of the patient)	Outcomes of blood and bile cultures	Baseline, pre-surgery, during the surgery, day 1, day 3
Post-operative pain	rate of patients who used the prescribed painkiller "to need"; average of daily administrations of painkillers prescribed "to need" in the first post-procedure day; rate of patients where postoperative pain management therapy had to be varied compared to protocol	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
• Investigators: Principal Investigator: Luca Ansaloni, MD, Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 22, 2025
• First Submitted That Met QC Criteria: April 1, 2025
• First Posted (Actual): April 9, 2025

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Gallbladder Diseases; Cholecystitis; Acalculous Cholecystitis; Cholecystitis, Acute
• Other Study ID Numbers: SETIMIHRACC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No