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

Sponsor

Hospital General Universitario de Alicante (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04924868

Collaborator

Instituto de Salud Carlos III (Other)

332

Enrollment

Locations

Arms

Anticipated Duration (Months)

18.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Pancreatitis Due to Gallstones	Drug: Ursodeoxycholic Acid Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

332 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Complication due to gallstones [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"

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Clínico Universitario de Santiago	Santiago De Compostela	A Coruña	Spain	15706
2	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
3	Hospital Universitario Central de Asturias.	Oviedo	Asturias	Spain	33011
4	Hospital de Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	08907
5	Consorci Corporació Sanitària Parc Taulí de Sabadell	Sabadell	Barcelona	Spain	08208
6	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
7	Hospital Costa del Sol,	Marbella	Málaga	Spain	29603
8	Clinica Unversidad de Navarra	Pamplona	Navarra	Spain	31008
9	Hospital Clínico Universitario de Valencia	Alicante	Valencia	Spain	46010
10	Hospital Universitario de Cruces	Bilbao	Vizcaya	Spain	48903
11	Hospital General Universitario de Alicante	Alicante		Spain	03010
12	Hospital Univerisitario Vall D´Hebron	Barcelona		Spain	08035
13	Hospital Clínio San Cecilio	Granada		Spain	18016
14	Hospital Ramon y Cajal	Madrid		Spain
15	Complejo Hospitalario de Ourense	Ourense		Spain	32005
16	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47003
17	Hospital Clínico Lozano Blesa	Zaragoza		Spain	50009
18	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009