Ursodeoxycolic Acid for the Prevention of Relapsing Complications After Gallstone Acute Pancreatitis, a Double-blind Multicenter Randomized-controlled Trial. OSOPOLAR Trial
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Hospital General Universitario de Alicante
- Enrollment
- 332
- Locations
- 18
- Primary Endpoint
- Complication due to gallstones
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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
Intervention: Ursodeoxycholic Acid (Drug)
Placebo group
Capsules containing placebo, indistinguishable from active treatment.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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"
Secondary Outcomes
- Relapse of acute pancreatitis(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- Incidence of acute cholecystitis(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 urgent cholecystectomy(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- EORTC-QLQ C30 questionnaire(Measurement at 1, 3, 6, 9 and 12 months after recruitment)
- Mortality(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- Incidence of acute cholangitis(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- Hospital stay during follow-up(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- Intensive care unit stay 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 during follow-up(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- Incidence of organ failure during follow-up(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- Incidence of biliary colic, with or without choledocholithiasis(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- Effectiveness of ursodeoxycholic acid in treating gallstones(Abdominal ultrasonography will be performed at 6 and 12 months after recruitment unless cholecystectomy is performed)
- Adverse events(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(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
- 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 surgical necrosectomy(From recruitment to cholecystectomy or up to 1 year after recruitment if cholecystectomy is not performed)
Investigators
Enrique de-Madaria
Coordinator of Biliary-Pancreatic Unit.
Hospital General Universitario de Alicante