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

Acute Pancreatitis Due to Gallstones Clinical Trial

— OSOPOLAR  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04924868
• Other study ID #: 2020/159
• Secondary ID: 2020-005901-16
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 1, 2021
• Est. completion date: July 1, 2025

Study information

• Verified date: June 2021
• Source: Hospital General Universitario de Alicante
• Contact: Alicia Vaillo
• Phone: (+34) 661302932
• Email: vailloalicia[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 332
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Pancreatitis Due to Gallstones
• Cholecystolithiasis
• Cholelithiasis
• Gallstones
• Pancreatitis

Intervention

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
Placebo: composition per 100g: colloidal silica 1.95g and cellulose microcrystalline 98.05g.

Locations

Country	Name	City	State
Spain	Hospital Clínico Universitario de Valencia	Alicante	Valencia
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Univerisitario Vall D´Hebron	Barcelona
Spain	Hospital Universitario de Cruces	Bilbao	Vizcaya
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Clínio San Cecilio	Granada
Spain	Hospital de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Costa del Sol,	Marbella	Málaga
Spain	Complejo Hospitalario de Ourense	Ourense
Spain	Hospital Universitario Central de Asturias.	Oviedo	Asturias
Spain	Clinica Unversidad de Navarra	Pamplona	Navarra
Spain	Consorci Corporació Sanitària Parc Taulí de Sabadell	Sabadell	Barcelona
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Clínico Universitario de Santiago	Santiago De Compostela	A Coruña
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Hospital Clínico Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Hospital General Universitario de Alicante	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complication due to gallstones	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	Relapse of acute pancreatitis	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
Secondary	Incidence of acute cholangitis	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
Secondary	Incidence of acute cholecystitis	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
Secondary	Incidence of biliary colic, with or without choledocholithiasis	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
Secondary	Effectiveness of ursodeoxycholic acid in treating gallstones	Decrease or elimination of gallstones according to ultrasonography	Abdominal ultrasonography will be performed at 6 and 12 months after recruitment unless cholecystectomy is performed
Secondary	EORTC-QLQ C30 questionnaire	EORTC-QLQ C30 questionnaire as a measure of Quality of Life	Measurement at 1, 3, 6, 9 and 12 months after recruitment
Secondary	Hospital stay during follow-up	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
Secondary	Intensive care unit stay during follow-up	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
Secondary	Adverse events	Adverse events due to ursodeoxycolic acid or placebo	From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Secondary	Number of visits to emergency room or hospital admissions due to symptomatic gallstone disease	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
Secondary	Need for endoscopic retrograde cholangio-pancreatography (ERCP) during follow-up	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
Secondary	Need for gallbladder endoscopic or percutaneous drainage during follow-up	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
Secondary	Need for drainage of collections and abscesses	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
Secondary	Incidence of organ failure during follow-up	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
Secondary	Mortality	Death during follow-up	From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed
Secondary	Need for urgent cholecystectomy	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
Secondary	Need for surgical necrosectomy	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