PrEveNtion of Biliary Events After Acute Pancreatitis in NonSUrgicaL PAtients: PENINSULA Trial

NCT06409741 | Enrolling By Invitation DMC

• 1 other identifier: CEIm Ref: 2023-139 (2023-414)
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 5

Brief Summary

Acute pancreatitis (AP) is a common condition and its main etiology is biliary. Cholecystectomy is the standard preventive treatment for recurrence of AP after admission. However, due to an increasingly older population and increased patient comorbidity, it is not always a possible option these days. If cholecystectomy is not performed, there is a significant risk for a recurrence of a biliopancreatic event (pancreatitis, biliary colic, choledocholithiasis, cholecystitis or cholangitis) of around 50% in the first year. This can lead to further episodes of pain, patient readmissions, and a reduced quality of life. Additionally, frequent readmissions can create a high cost burden on the health system. Currently, certain clinical guidelines propose biliary sphincterotomy as an alternative for patients in whom surgery is not feasible. However, this recommendation is based on retrospective studies with small sample size and the adherence to this recommendation is very low (12-23%). The goal of this clinical trial is to evaluate the recurrence of biliopancreatic events in the first year after admission for an acute biliary pancreatitis episode in patients that are not suitable for surgery. The main question it aims to answer is: Does biliary sphincterotomy prevent biliopancreatic event recurrence in non surgical patients after an episode of biliary acute pancreatitis? Researchers will compare biliary sphincterotomy vs conservative treatment to see if there is a reduction in biliopancreatic events during the first year after admission for acute pancreatitis in non surgical patients. Participants will be randomized to conservative treatment or biliary sphincterotomy and will be followed up for one year at 1 month, 6 months and 12 months to evaluate recurrence of BPE, readmissions, quality of life and mortality. Security of the technique will also be assessed in this specific population.

Conditions

Acute Pancreatitis Due to Gallstones; Acute Pancreatitis

Keywords

sphincterotomy; acute pancreatitis; recurrence; conservative treatment; biliopancreatic events

Outcome Measures

Primary Outcomes (1)

• Biliopancreatic events (BPE)

  The primary aim is to assess the recurrence of the combined variable of biliopancreatic events (biliary colic, cholangitis, choledocholithiasis, acute cholecystitis or AP) of the endoscopic sphincterotomy strategy during the follow-up time after diagnosis of AP of biliary origin in inoperable patients with respect to conservative treatment.

  From enrollment until 12 months after

Secondary Outcomes (13)

• Time to recurrence of BPE

  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

• Technical success of biliary sphincterotomy

  From enrollment until one month after

• Sphincterotomy related adverse events

  From enrollment until one month after

• Emergency room visits (BPE related)

  From enrollment until 12 months after

Study Arms (2)

Biliary sphincterotomy

ACTIVE COMPARATOR

In the group assigned to receive endoscopic treatment, ERCP for biliary sphincterotomy will be performed during the index admission for acute pancreatitis, prior to discharge or up till one month from discharge. The procedure will be performed after at least 6 hours of fasting during the index admission, by endoscopists in charge of performing ERCP as usual in the collaborating centers under sedation controlled by endoscopists or anesthesia according to the usual practice of the Endoscopy Unit of each collaborating center. For ERCP biliary cannulation, the usual techniques available in each center will be used, including advanced cannulation techniques if necessary. If biliary cannulation is not possible, a new ERCP attempt will be performed within a maximum of one month. If biliary cannulation is still not achieved, it will be counted as a technical failure.

Procedure: Biliary sphincterotomy

Conservative treatment

NO INTERVENTION

Patients allocated to this group will be discharged without any intervention. The inhospital management of patients with AP in the conservative treatment group, before and after randomization, will be under the care of their responsible physicians on the hospitalization wart at the corresponding collaborating center who will follow the management recommended by the clinical guidelines. Their discharge will be decided by their regular physician. Patients will be evaluated at one month, six months and one year and both clinical variables (clinical BPE recurrence) and quality of life will be assessed (quality of life by a survey- EORTC QLQ-C30,

Interventions

Biliary sphincterotomy PROCEDURE

ERCP for biliary sphincterotomy will be performed during index admission for acute pancreatitis, prior to discharge or up till one month from discharge. The procedure will be performed after at least 6 hours of fasting during the index admission, by endoscopists in charge of performing ERCP as usual in the collaborating centers under sedation controlled by endoscopists or anesthesia according to the usual practice of the Endoscopy Unit of each collaborating center. For ERCP biliary cannulation, the usual techniques available in each center will be used, including advanced cannulation techniques if necessary. If biliary cannulation is not possible, a new ERCP attempt will be performed within a maximum of one month. If biliary cannulation is still not achieved, it will be it will be counted as a technical failure, maintaining the established clinical follow-up.

Biliary sphincterotomy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient older than 18 years old.
• Definitive diagnosis of acute pancreatitis according to the presence of two out of three criteria from the Revised Atlanta Classification. At least 2 criteria: A) Typical pain, B) Amylase or lipase ≥x3 normal limit, C) Imaging evidence compatible with acute pancreatitis).
• Biliary etiology: (any imaging test that describes gallbladder lithiasis/microlithiasis or biliary sludge).
• Magnetic resonance cholangiography (MRCP) or endoscopic ultrasound (EUS) is required without evidence of choledocholithiasis.
• Surgical decision of inoperable patient (if meets one or more of the following criteria: age ≥ 80 years, American Society of Anesthesiology (ASA) III or more, Charlson Comorbidity Index \> 5 and/or Karnofsky \< 50 or patient's decision not to undergo surgery. Patient must have been evaluated by general surgery or anesthesia.
• Signature of the informed consent for the study

You may not qualify if:

• Patient refusal to participate in the study.
• Active ethylism greater than or equal to 5 drinking units per day in men and 3 in women or strong clinical suspicion of clinically significant ethylism that could be a cause of their AP.
• Hypertriglyceridemia greater than 400 mg/dl at admission or history of poorly controlled hypertriglyceridemia.
• Chronic pancreatitis: pancreatic calcifications in body or Wirsung on imaging or Wirsung ≥ 4 mm
• Biliary condition requiring sphincterotomy during index admission (cholangitis or symptomatic choledocholithiasis) or previous biliary sphincterotomy.
• Previous cholecystectomy
• Actual use of ursodeoxycholic acid
• Gastrointestinal tract anatomy altered by previous hepatobiliary or upper gastrointestinal surgery.
• Inability to tolerate endoscopy sedation, perforation of the digestive tract or other contraindication to endoscopy.
• Coagulopathy with uncorrectable International Normalized Ratio \> 1.5 or uncorrectable thrombocytopenia \< 50000/mm3.
• Other concomitant diagnoses on admission (liver abscesses, biliopancreatic neoplasia, acute cholecystitis).
• Hemodynamic instability.
• Baseline ECOG ≥4

Sponsors & Collaborators

• Hospital General Universitario de Alicante: lead
• Hospital Universitario Ramon y Cajal: collaborator
• Hospital del Rio Hortega: collaborator
• Hospital Universitario Reina Sofia de Cordoba: collaborator
• Hospital Clínico Universitario de Valencia: collaborator

Study Sites (5)

Hospital General Universitario Dr. Balmis

Alicante, Alicante, 03010, Spain

Location

Hospital Universitaria Reina Sofía

Córdoba, Cordoba, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Spain

Location

Hospital Clinico Universitairo

Valencia, Valencia, Spain

Location

Hospital Universitario Río Hortega

Valladolid, Valladolid, Spain

Location

MeSH Terms

Conditions

Pancreatitis; Recurrence

Interventions

Sphincterotomy, Endoscopic

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biliary Tract Surgical Procedures; Digestive System Surgical Procedures; Surgical Procedures, Operative; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Endoscopy; Minimally Invasive Surgical Procedures; Sphincterotomy; Myotomy

Study Officials

• José R Aparicio, MD

  Hospital General Universitario Dr. Balmis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Chief of Endoscopy Unit

Study Record Dates

• First Submitted: May 5, 2024
• First Posted: May 10, 2024
• Study Start: December 16, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 1, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5)