Clinical trial NCT06364397: Efficacy of ERCP in the Diagnosis and Treatment of Idiopathic Recurrent Acute Pancreatitis
Official title: Efficacy of ERCP in the Diagnosis and Treatment of Idiopathic Recurrent Acute Pancreatitis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Recurrent Acute Pancreatitis
Keywords: Recurrent acute pancreatitis
Idiopathic
ERCP
Sphincterotomy
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
Collaborators: name: Peking Union Medical College Hospital
name: First People's Hospital of Hangzhou
First posted: 2024-04-15
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if endoscopic retrograde cholangiopancreatography (ERCP) works to treat idiopathic recurrent pancreatitis (IRAP) in adults. It also clarify the efficacy of ERCP in the diagnosis of IRAP. The main questions it aims to answer are:

Does ERCP reduce the frequency of pancreatitis episodes in IRAP patients? Does ERCP contribute to identify the etiology of IRAP patients?

Participants will be randomly allocated to receive ERCP (pancreatic sphincterotomy and pancreatic stent placement) or conservative treatment and be followed for 1 year.

Detailed description: Recurrent acute pancreatitis (RAP) is defined as 2 or more distinct episodes of acute pancreatitis (AP) with complete resolution between each episode, and absence of irreversible structural and functional changes in pancreas. RAP has an estimated annual incidence of 8-10 per 100,000 and the recurrence rate is as high as 10-30% in AP patients. At present, biliary, alcoholic and hypertriglyceridemia are common causes of RAP. There are also a variety of causes that may contribute to recurrent episodes of AP, such as gene mutations, pancreas divisum, ampullary neoplasms and sphincter of Oddi dysfunction. About 80% of RAP patients can be identified through routine clinical investigations (include proper history, physical examination, imaging examination); however, the etiology in up to 20% of cases still not be clarified and these patients is called idiopathic recurrent acute pancreatitis (IRAP).

Endoscopic retrograde cholangiopancreatography (ERCP) is an important minimally invasive treatment for pancreatic diseases. However, the role of ERCP in IRAP patients with normal biliary and pancreatic anatomy remains controversial and there is a lack of high-quality clinical research evidence on endoscopic treatment of IRAP. In a small sample size (N=34) open-label randomized controlled study, IRAP patients were assigned to the experimental group with pancreatic duct stent placement and the control group with selective pancreatograms but no stent. This study demonstrated that stent placement was able to reduce the recurrence rate of AP (53% vs 11%, P \< 0.02). Coté et al performed an open-label randomized trial (N=89) of ERCP with sphincter of Oddi manometry for IRAP patients. Among patients with pancreatic sphincter dysfunction, they found that biliary sphincterotomy and combination of biliary and pancreatic sphincterotomy have similar effects in preventing recurrence of AP, and there was also no significant difference between biliary sphincterotomy and sham surgery in patients with normal sphincter of Oddi manometry. However, some retrospective studies had shown that sphincterotomy works to reduce the recurrence rate of acute pancreatitis.

Currently, there is a shortage of high-quality evidence, and the wide variation in different study designs has led to controversial conclusions. Given the long-standing controversy, we propose to conduct a randomized controlled trial to investigate the efficacy of ERCP in the diagnosis and treatment of Idiopathic recurrent acute pancreatitis.

Eligibility criteria: Inclusion Criteria:

1. Aged 18 to 70 years.
2. Patients diagnosed with IRAP:

   1. Previously experienced 2 or more distinct episodes of acute pancreatitis (AP) with complete resolution between each episode, and absence of irreversible structural and functional changes in pancreas. The diagnosis of AP is based on the Atlanta criteria and is documented in the medical record.
   2. The etiology of RAP remains undetermined after routine clinical investigations, including history, laboratory examination, imaging examination (CT, MRI/MRCP, EUS). Patients who still have AP episodes after elimination of the etiology also be included.
3. At least 1 episode of AP one year prior to enrollment.
4. Consent to participate in the study and sign the informed consent form.

Exclusion Criteria:

1. Prior sphincter intervention.
2. Not recovered from prior AP attack.
3. Prior pancreatic surgery.
4. Contraindications to ERCP.
5. Major mental illness or serious health problems that are not suitable for participation in the study.
6. Pregnancy or plan for pregnancy within 12 months of enrollment.
7. Other conditions that inappropriate to participant in the study.

Primary outcomes:
measure: Recurrence rate of AP
timeFrame: 1 year after enrollment
Secondary outcomes:
measure: Ratio of reduced AP episodes
timeFrame: 1 year after enrollment
measure: Proportion of patients with reduced AP episodes
timeFrame: 1 year after enrollment
measure: Severity of AP
timeFrame: 1 year after enrollment
measure: Evaluation of quality of life
timeFrame: 1 year after enrollment
measure: Evaluation of psychological condition
timeFrame: 1 year after enrollment
measure: Proportion of patients diagnosed by ERCP.
timeFrame: 1 year after enrollment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
affiliation: Changhai Hospital
name: Zhaoshen Li, M.D.
role: STUDY_CHAIR
References:
citation: Guda NM, Trikudanathan G, Freeman ML. Idiopathic recurrent acute pancreatitis. Lancet Gastroenterol Hepatol. 2018 Oct;3(10):720-728. doi: 10.1016/S2468-1253(18)30211-5.
citation: Machicado JD, Yadav D. Epidemiology of Recurrent Acute and Chronic Pancreatitis: Similarities and Differences. Dig Dis Sci. 2017 Jul;62(7):1683-1691. doi: 10.1007/s10620-017-4510-5. Epub 2017 Mar 9.
citation: Sankaran SJ, Xiao AY, Wu LM, Windsor JA, Forsmark CE, Petrov MS. Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis. Gastroenterology. 2015 Nov;149(6):1490-1500.e1. doi: 10.1053/j.gastro.2015.07.066. Epub 2015 Aug 20.
citation: Ahmed Ali U, Issa Y, Hagenaars JC, Bakker OJ, van Goor H, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Brink MA, Schaapherder AF, Dejong CH, Spanier BW, Heisterkamp J, van der Harst E, van Eijck CH, Besselink MG, Gooszen HG, van Santvoort HC, Boermeester MA; Dutch Pancreatitis Study Group. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis. Clin Gastroenterol Hepatol. 2016 May;14(5):738-46. doi: 10.1016/j.cgh.2015.12.040. Epub 2016 Jan 6.
citation: Jacob L, Geenen JE, Catalano MF, Geenen DJ. Prevention of pancreatitis in patients with idiopathic recurrent pancreatitis: a prospective nonblinded randomized study using endoscopic stents. Endoscopy. 2001 Jul;33(7):559-62. doi: 10.1055/s-2001-15314.
citation: Cote GA, Imperiale TF, Schmidt SE, Fogel E, Lehman G, McHenry L, Watkins J, Sherman S. Similar efficacies of biliary, with or without pancreatic, sphincterotomy in treatment of idiopathic recurrent acute pancreatitis. Gastroenterology. 2012 Dec;143(6):1502-1509.e1. doi: 10.1053/j.gastro.2012.09.006. Epub 2012 Sep 11.
citation: Strand DS, Law RJ, Yang D, Elmunzer BJ. AGA Clinical Practice Update on the Endoscopic Approach to Recurrent Acute and Chronic Pancreatitis: Expert Review. Gastroenterology. 2022 Oct;163(4):1107-1114. doi: 10.1053/j.gastro.2022.07.079. Epub 2022 Aug 22.
citation: Wehrmann T. Long-term results (>/= 10 years) of endoscopic therapy for sphincter of Oddi dysfunction in patients with acute recurrent pancreatitis. Endoscopy. 2011 Mar;43(3):202-7. doi: 10.1055/s-0030-1255922. Epub 2010 Nov 24.