Ursodeoxycolic Acid for the Prevention of Relapsing Complications After Gallstone Acute Pancreatitis (OSOPOLAR)

March 16, 2025 updated by: Enrique de-Madaria, Hospital General Universitario de Alicante

Ursodeoxycolic Acid for the Prevention of Relapsing Complications After Gallstone Acute Pancreatitis, a Double-blind Multicenter Randomized-controlled Trial. OSOPOLAR Trial

Acute pancreatitis is a common disease (3rd cause of hospital admission for digestive causes), which is associated with significant patient suffering, a 2-4% probability of death and considerable healthcare costs. Sixty percent of acute pancreatitis are due to the presence of stones in the gallbladder. The risk of suffering another acute biliary pancreatitis (ABP, that is to say, pancreatitis due to gallstones) or of other biliary complications in the following weeks or months is high (20% or greater) if measures are not taken to avoid it, being surgical removal of the gallbladder the most effective. Unfortunately, most Spanish centers have a surgical waiting list that makes gallbladder surgery unfeasible in a period of less than weeks or months, which is why readmission for biliary problems derived from the stones is a common problem. This, of course, causes danger and great stress and anger for patients affected by these complications on the waiting list, damaging their relationship with the health system and it is linked to increased cost. In addition, there is a very vulnerable group, those patients who due to age or serious diseases cannot undergo gallbladder surgery but have a high probability of suffering biliary problems due to the stones they have.

Ursodeoxycholic acid (UDCA) is very safe drug which is used to dissolve gallstones, but its role in preventing biliary complications after ABP has not been studied adequately so it is not frequently used. Our objective is to investigate if UDCA is useful in this scenario, which would avoid suffering and adverse consequences for the patient and reduce the consumption of resources.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

332

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Spain
      • Alicante, Spain, 03010
        • Recruiting
        • Hospital General Universitario de Alicante
        • Contact:
        • Contact:
          • Enrique de Madaria, Medicine
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Hospital Univerisitario Vall D´Hebron
        • Contact:
        • Contact:
          • Francesc Xa Molero Richard, Medicine
      • Granada, Spain, 18016
        • Not yet recruiting
        • Hospital Clínio San Cecilio
        • Contact:
        • Contact:
          • Antonio M Caballero, Medicine
      • Madrid, Spain
        • Recruiting
        • Hospital Ramon y Cajal
        • Contact:
        • Contact:
          • Ana García García de Paredes
      • Ourense, Spain, 32005
        • Not yet recruiting
        • Complejo Hospitalario de Ourense
        • Contact:
        • Contact:
          • Maria Francisco González, Medicine
      • Valladolid, Spain, 47003
        • Recruiting
        • Hospital Clinico Universitario de Valladolid
        • Contact:
        • Contact:
          • Maria Lo Ruíz Rebollo
      • Zaragoza, Spain, 50009
        • Not yet recruiting
        • Hospital Universitario Miguel Servet
        • Contact:
        • Contact:
          • Vanesa Bernal Monterde, Medicine
      • Zaragoza, Spain, 50009
        • Recruiting
        • Hospital Clinico Lozano Blesa
        • Contact:
        • Contact:
          • Guillermo García Rayado, Medicine
    • A coruña
      • Santiago De Compostela, A coruña, Spain, 15706
        • Not yet recruiting
        • Hospital Clínico Universitario de Santiago
        • Contact:
        • Contact:
          • Juan En Domínguez Muñoz
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Not yet recruiting
        • Hospital General Universitario de Elche
        • Contact:
        • Contact:
          • Irene Pascual Sánchez, Medicine
    • Asturias
      • Oviedo, Asturias, Spain, 33011
        • Recruiting
        • Hospital Universitario Central de Asturias.
        • Contact:
        • Contact:
          • Maria Eu Lauret Braña, Medicine
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Not yet recruiting
        • Hospital De Bellvitge
        • Contact:
        • Contact:
          • Silvia Salord Vila, Medicine
      • Sabadell, Barcelona, Spain, 08208
        • Not yet recruiting
        • Consorci Corporació Sanitària Parc Taulí de Sabadell
        • Contact:
        • Contact:
          • Laura Pa Llovet Soto, Medicine
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Not yet recruiting
        • Hospital Universitario Marqués de Valdecilla
        • Contact:
        • Contact:
          • Claudia Sánchez Marín, Medicine
    • Málaga
      • Marbella, Málaga, Spain, 29603
        • Recruiting
        • Hospital Costa del Sol,
        • Contact:
        • Contact:
          • Robin Rivera Irigoin, Medicine
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Recruiting
        • Clinica Unversidad de Navarra
        • Contact:
        • Contact:
          • Cristina Carretero Ribón, Medicine
    • Valencia
      • Alicante, Valencia, Spain, 46010
        • Recruiting
        • Hospital Clínico Universitario de Valencia
        • Contact:
        • Contact:
          • Isabel Pascual Moreno, Medicine
    • Vizcaya
      • Bilbao, Vizcaya, Spain, 48903

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 years old or older
  • Hospital admission due to acute pancreatitis (definition: at least 2 of the following criteria: A) Typical pancreatitis pain, B) Amylase and/or lipase higher than 3 times the upper level of normality, C) Imaging compatible with acute pancreatitis
  • Presence of gallstones according to any imaging technique
  • Patient informed consent

Exclusion Criteria:

  • Cholecystectomy and/or endoscopic retrograde cholangio-pancreatography and / or endoscopic cholecystostomy prior to recruitment
  • Recurrent acute pancreatitis (1 or more previous episodes of pancreatitis of any origin)
  • Current waiting list for cholecystectomy for acute biliary pancreatitis at that center less than 30 days
  • Randomization more than 3 days after hospital discharge for acute pancreatitis
  • Ursodeoxycholic acid (UDCA) consumption in the last 5 years or previous UDCA failure to dissolve lithiasis
  • Allergy, intolerance or presence of contraindications to UDCA (contraindicated in patients with active gastric or duodenal ulcer, liver or intestinal disorders that interfere with the enterohepatic circulation of bile salts and lactation)
  • Presence of choledocholithiasis diagnosed by imaging tests prior to randomization
  • Active alcoholism greater than or equal to 5 daily alcoholic drinks in men or 3 in women or high clinical suspicion of clinically significant alcoholism
  • Recent history of significant therapeutic non-compliance or social problem that makes follow-up difficult
  • Hypertriglyceridemia greater than 400 mg / dL during admission or history of poorly controlled severe hypertriglyceridemia
  • Chronic pancreatitis (pancreatic calcifications and / or Wirsung duct 4 or more mm)
  • Pancreatic cystic lesions not attributed to the pancreatitis itself
  • Wirsung duct stenosis
  • Primary hyperparathyroidism
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: UDCA (Ursodeoxycholic Acid) group

Patients receiving Ursodeoxycholic Acid, capsules containing 300 mg, 10 mg/Kg per day:

Patients 40 to 70 kg: 2 capsules/day >70 to 100 Kg: 3 capsules/day >100 kg: 4 capsules/day
Drug: Ursodeoxycholic Acid
Ursodeoxycholic Acid will be administered to patients in the UDCA group as a prophylactic measure of future complications associated to gallstones
Placebo Comparator: Placebo group
Capsules containing placebo, indistinguishable from active treatment.
Drug: Placebo
Placebo: composition per 100g: colloidal silica 1.95g and cellulose microcrystalline 98.05g.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complication due to gallstones
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Composite endpoint: incidence of any of the following: acute pancreatitis, acute cholangitis, acute cholecystitis, biliary colic (with or without choledocholithiasis) Definitions are provided in "Secondary Outcome Measures"
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse of acute pancreatitis
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
New episode of acute pancreatitis after recruitment Definition of acute pancreatitis (revised Atlanta classification): 2 or more of the following criteria: A) Typical pancreatitis pain, B) Amylase and/or lipase higher than 3 times the upper level of normality, C) Imaging compatible with acute pancreatitis
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Incidence of acute cholangitis
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed

Acute cholangitis after recruitment

Acute cholangitis definition (Tokyo 2018 guidelines):

A. Systemic inflammation: A-1. Fever and/or shaking chills; A-2. Laboratory data: evidence of inflammatory response B. Cholestasis: B-1. Jaundice; B-2. Laboratory data: abnormal liver function tests C. Imaging: C-1. Biliary dilatation; C-2. Evidence of the etiology on imaging (stricture, stone, stent etc.) Suspected diagnosis: one item in A + one item in either B or C Definite diagnosis: one item in A, one item in B and one item in C
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Incidence of acute cholecystitis
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed

Acute cholecystitis after recruitment

Acute cholecystitis definition (Tokyo 2018 guidelines):

A. Local signs of inflammation: (1) Murphy's sign, (2) RUQ mass/pain/tenderness B. Systemic signs of inflammation: (1) Fever, (2) elevated CRP, (3) elevated WBC count C. Imaging findings: Imaging findings characteristic of acute cholecystitis Suspected diagnosis: one item in A + one item in B Definite diagnosis: one item in A + one item in B + C
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Incidence of biliary colic, with or without choledocholithiasis
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Biliary colic after recruitment Biliary colic definition: typical biliary colic pain. Choledocholithiasis: presence of stones or biliary sludge in the common bile duct according to imaging or endoscopic retrograde cholangio-pancreatography
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Effectiveness of ursodeoxycholic acid in treating gallstones
Time Frame: Abdominal ultrasonography will be performed at 6 and 12 months after recruitment unless cholecystectomy is performed
Decrease or elimination of gallstones according to ultrasonography
Abdominal ultrasonography will be performed at 6 and 12 months after recruitment unless cholecystectomy is performed
EORTC-QLQ C30 questionnaire
Time Frame: Measurement at 1, 3, 6, 9 and 12 months after recruitment
EORTC-QLQ C30 questionnaire as a measure of Quality of Life
Measurement at 1, 3, 6, 9 and 12 months after recruitment
Hospital stay during follow-up
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Number of days admitted due to symptomatic gallstone disease
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Intensive care unit stay during follow-up
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Number of days admitted in the intensive care unit due to symptomatic gallstone disease
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Adverse events
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Adverse events due to ursodeoxycolic acid or placebo
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Number of visits to emergency room or hospital admissions due to symptomatic gallstone disease
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Number of visits to emergency room or hospital admissions due to symptomatic gallstone disease
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for endoscopic retrograde cholangio-pancreatography (ERCP) during follow-up
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for ERCP due to choledocholithiasis or acute cholangitis
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for gallbladder endoscopic or percutaneous drainage during follow-up
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for gallbladder endoscopic or percutaneous drainage due to acute cholecystitis or cholangitis
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for drainage of collections and abscesses
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for drainage of collections and abscesses (liver abscess, symtomatic pancreatic or peripancreatic collections not related to the index acute pancreatitis)
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Incidence of organ failure during follow-up
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Organ failure definition (revised Atlanta classification): PaO2/FIO2<300, Creatinine >=1.9 mg/dl and/or systolic blood pressure <90mmHg despite fluid resuscitation
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Mortality
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Death during follow-up
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for urgent cholecystectomy
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for urgent cholecystectomy for acute gallbladder complication, mainly acute cholecystitis
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for surgical necrosectomy
Time Frame: From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Need for surgical necrosectomy, mainly after infection of pancreatic necrosis (not related to the index acute pancreatitis)
From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital General Universitario de Alicante

Collaborators

Instituto de Salud Carlos III

Investigators

  • Principal Investigator: Enrique De Madaria, Medicine, Alicante General University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 10, 2021

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

June 8, 2021

First Submitted That Met QC Criteria

June 8, 2021

First Posted (Actual)

June 14, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 16, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020/159
  • 2020-005901-16 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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