Conservative Versus Proactive Management of Acute Cholecystitis After EUS-guided Transmural Gallbladder Drainage. Multicenter Randomized Clinical Trial: FUGITIVE Trial (FUGITIVE)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 82
- Locations
- 2
- Primary Endpoint
- Biliopancreatic events (BPE)
Study Overview
Brief Summary
Patients with gallbladder inflammation (acute cholecystitis) who cannot undergo surgery due to their fragility and surgical risk require a gallbladder drainage. It has been confirmed in previous studies that the gallbladder drainage from the digestive tract is a better alternative, because it has fewer complications than external (percutaneous) gallbladder drainage. However, there are no known studies that demonstrate whether it is better to maintain this drainage indefinitely, or to carry out periodic revisions of the drainage to progressively remove the stones lodged in the gallbladder and remove the drainage once this has been achieved. In this study we aim to compare the clinical evolution of patients who undergo this gallbladder drainage, dividing them into two groups:
- One group of patients in whom we maintain a metallic prosthesis or stent, which communicates the gallbladder with the stomach, indefinitely in order to always guarantee a drainage of the bile towards the digestive tract, and thus avoid new episodes of cholecystitis.
- Another group of patients who, one month after having undergone drainage, undergo a new procedure to remove the gallbladder lithiasis, until it is empty and without inflammation and we can remove the metal stent, leaving only a very thin plastic catheter to maintain the fistula and thus the bile continues to flow into the digestive tract. More than one procedure may be required to completely clear the gallbladder.
Knowledge of whether one strategy or the other presents fewer complications in the short, medium and long term is essential to be able to offer the best alternative to our patients.
The aim of the study is to compare the clinical outcome of these patients who have a definitive drain inserted with those who undergo several procedures to clear the gallbladder until the drain is removed. The rate of complications, the need for re-interventions and hospital admissions, new episodes of acute cholecystitis, quality of life and mortality of both groups over a period of one year are compared.
Detailed Description
Laparoscopic cholecystectomy is the gold standard for treating acute cholecystitis (AC). However, not all patients are suitable candidates for surgery during an AC episode. After recovery, some may improve sufficiently to undergo preventive surgery for future biliary events, while others remain high-risk surgical candidates or fail to recover adequately, making surgery infeasible. For these high-risk patients, optimal management remains uncertain. Currently, percutaneous drainage is the standard treatment, with endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) emerging as a viable alternative in specialized centers. Recent data suggest that EUS-GBD may result in fewer complications compared to percutaneous drainage, with similar technical and clinical success rates.
Despite its promise, the optimal follow-up strategy for patients treated with EUS-GBD remains unclear, particularly regarding long-term complications associated with lumen-apposing metal stents (LAMS). Studies in pancreatic fluid collections suggest higher rates of complications, including bleeding and stent obstruction, leading to recommendations for early stent removal. However, for gallbladder drainage, the question arises whether LAMS should be maintained to prevent recurrence or replaced with less complication-prone stents like double pigtail stents.
The available evidence is contradictory. Some studies favor proactive endoscopic follow-up and gallstone removal to minimize recurrent cholecystitis, while others suggest that leaving LAMS indefinitely may reduce biliary events and hospital visits. To resolve these discrepancies, randomized prospective trials are needed to determine the optimal follow-up protocol for high-risk patients undergoing EUS-GBD for AC.
Our working hypothesis is that after EUS-GBD using a LAMS, there are no significant differences in the rate of biliopancreatic events between an active endoscopic approach (including gallbladder cleaning, stone extraction, and stent removal) and a conservative approach (without planned endoscopic interventions). Some studies even suggest that the proactive approach may lead to more complications The primary aim is to compare the rate of biliopancreatic events during one year of follow-up between patients treated with a proactive endoscopic strategy (group A) and those treated with a conservative strategy (group B) after EUS-GBD for acute cholecystitis (AC).
Secondary objectives focus on the evaluation of additional clinical outcomes, including complication rates at various time points, recurrence of biliary-related events, unplanned re-interventions, readmissions, mortality, disease-free survival, resolution of AC, and quality of life between the two groups.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient ≥ 18 years of age
- •Confirmed acute cholecystitis diagnosed according to Tokyo 2018 criteria.
- •Patient unfit for surgery: if meets one or more of the following criteria: age ≥ 80 years, American Society of Anesthesiology (ASA) ≥ III, Charlson Comorbidity Index > 5 and/or Karnofsky < 50, or patient unwilling to undergo surgery.
- •Gallbladder drainage by LAMS stent.
- •Informed Consent signed
Exclusion Criteria
- •Patient refusal to participate in the study
- •Gastrointestinal surgically modified anatomy preventing endoscopic access to the gallbladder.
- •Technical failure to perform endoscopic ultrasound guided-gallbladder drainage.
- •Moderate or severe ascites.
- •Severe coagulopathy International Normalized Ratio >1.5 and/or fibrinogen <120) or thrombocytopenia (platelets <20,000).
- •Patient unable to tolerate sedation or general anesthesia
- •Haemodynamically unstable patient
- •Life expectancy <6 months
- •Baseline ECOG ≥4
- •Patient with ongoing malignancy
- •Pregnancy
- •Acute pancreatitis
Arms & Interventions
Cholecystoscopy, gallbladder cleaning and removal of lumen-apposing metal stent
Elective upper gastrointestinal endoscopy to perform cholecystoscopy, cleaning and removal of gallbladder (GB) stones and retrieval of the Lumen Apposing Metal Stent (LAMS) will be conducted 1 month after endoscopic ultrasound-guided GB drainage. For persistent GB stones, consecutive procedures will be performed weekly until complete cleaning and retrieval of the LAMS. A coaxial double pigtail plastic stent (7 or 10 Fr x 3 cm) will be placed indefinitely to maintain the fistula between the GB and the digestive tract.
Intervention: Cholecystoscopy and gallbladder cleaning (Procedure)
Conservative treatment: Indwelling stent
Patients in the conservative group will not be scheduled for endoscopic revision during the one-year follow-up. The LAMS will only be reviewed as part of routine practice for suspected LAMS related complications
Outcomes
Primary Outcomes
Biliopancreatic events (BPE)
Time Frame: From enrollment until 12 months after
The primary aim is to assess the difference in terms of recurrence of the combined variable of biliopancreatic events (biliary colic, cholangitis, choledocholithiasis, acute cholecystitis or acute pancreatitis) between the active treatment group and the conservative treatment group during follow-up period.
Secondary Outcomes
- Mortality rate(From enrollment until 12 months after)
- Disease-Free survival(From enrollment until 12 months after)
- Recurrence rate of cholecystitis(From enrollment until 12 months after)
- Biliary cause admission rate(From enrollment until 12 months after)
- Recurrence of each of the variables that make up the combined variable BPE separately(From enrollment until 12 months after)
- Total complication rate(From enrollment until 12 months after)
- Unplanned reintervention rate(From enrollment until 12 months after)
- Clinical Success Rate for the Resolution of Cholecystitis(From enrollment until 12 months after)
Investigators
Jose Ramon Aparicio Tormo
MD
Hospital General Universitario de Alicante