The hypothesis is that obstruction at the level of the minor papilla is one cause of RAP in pancreas divisum; miES will relieve the obstruction, thereby reducing the risk of a recurrent attack(s) of acute pancreatitis.
ID
Source
Brief title
Condition
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1.Reduce the risk of subsequent acute pancreatitis:
To test this aim, compare the incidence of acute pancreatitis > 30 days after
treatment allocation as the primary outcome measure, using the next attack of
acute pancreatitis as a time-to-event outcome.
Secondary outcome
Incidence rate ratio.
Patient-reported outcomes
Progression to chronic pancreatitis
Biorepository
Background summary
ERCP is a moderately high-risk intervention that has unproven benefit for
patients with iRAP. However, based on predominantly retrospective cohort
studies and the notion that pancreas divisum anatomy predisposes some patients
to acute pancreatitis, minor papilla endoscopic sphincterotomy (miES) is
commonly performed in clinical practice. Although the technique of miES has
been performed for >30 years, there has
been only one pilot, open-label, randomized trial of 19 patients with iRAP
published over 20 years ago.(Lans, Geenen et al. 1992) This study compared
serial dilation of the minor papillary orifice via pancreatic stents - a
surrogate for miES - vs. diagnostic ERCP. After mean follow-up of 29-32 months,
6/9 (67%) patients who underwent diagnostic only ERCP developed at least one
bout of acute pancreatitis as compared to
1/10 (10%, p<0.05) that underwent serial pancreatic duct stent placement.
Serial stent placement has been replaced by miES in clinical practice since
serial stenting requires multiple ERCPs and increases the risk of
stent-associated main duct strictures.
Several retrospective cohort studies also support the practice of miES for RAP
in the setting of pancreas divisum, with >70% of patients in most studies
reporting a significant improvement in their disease course (Gerke, Byrne et
al. 2004, Attwell, Borak et al. 2006, Chacko, Chen et al. 2008, Borak,
Romagnuolo et al. 2009, Crino, Bernardoni et al. 2017). While supporting the
role of miES, these studies chose a subjective endpoint
(self-perceived improvement) despite their open-label design and absence of a
sham comparison group. The controversy is a recurrent topic at national
meetings, and opposite positions were nicely summarized after a debate at the
2006 meeting of the American Pancreatic Association (Fogel, Toth et al. 2007).
Both sides acknowledged the need for randomized trials, yet there has been
little progress in clarifying the benefit
of miES on iRAP with pancreas divisum over the past decade.
Study objective
The hypothesis is that obstruction at the level of the minor papilla is one
cause of RAP in pancreas divisum; miES will relieve the obstruction, thereby
reducing the risk of a recurrent attack(s) of acute pancreatitis.
Study design
This is a sham-controlled, single blinded with a blinded outcome assessment,
multi-center, randomized clinical trial of endoscopic retrograde
cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy
(miES) for the treatment of recurrent acute pancreatitis (RAP) with pancreas
divisum. ERCP with miES is often offered in clinical practice to patients with
RAP, pancreas divisum, and no other clear risk factors for their acute
pancreatitis episodes. The trial requires a total sample size of approximately
234 subjects, and a planned enrollment period of approximately 3.5 years with
total planned study duration of 5 years (minimum follow-up of 6 months, maximum
follow-up of 48 months).
Intervention
Sham Comparator: EUS + Sham
Experimental: EUS + ERCP with miES
Study burden and risks
.
Ashley Ave 179
Charleston SC 29425-8908
US
Ashley Ave 179
Charleston SC 29425-8908
US
Listed location countries
Age
Inclusion criteria
1.Patient must consent to be in the study and must have signed and dated an
approved consent form.
2.>18 years
3.Two or more episodes of acute pancreatitis, with each episode meeting two of
the following three criteria:
*abdominal pain consistent with acute pancreatitis (acute onset of a
persistent, severe, epigastric pain often radiating to the back)
*serum lipase activity (or amylase activity) at least three times greater than
the upper limit of normal
*characteristic findings of acute pancreatitis on CECT, MRI or transabdominal
ultrasonography4.At least one episode of acute pancreatitis within 24 months of
enrollment
5.Pancreas divisum confirmed by prior MRCP that is reviewed by an abdominal
radiologist at the recruiting site.
6.By physician assessment, there is no certain explanation for recurrent acute
pancreatitis.
7.Subjects must be able to fully understand and participate in all aspects of
the study, including completion of questionnaires and telephone interviews, in
the opinion of the clinical investigator
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Exclusion criteria
Exclusion Criteria:
1.Prior minor papilla therapy (endoscopic or surgical)
2.Calcific chronic pancreatitis, defined as parenchymal or ductal
calcifications identified on computed tomography or magnetic resonance imaging
scan that is reviewed by an expert radiologist at the recruiting site.
3.Main pancreatic duct stricture*
4.Presence of a structural etiology for acute pancreatitis, such as anomalous
pancreatobiliary union, periampullary mass, or pancreatic mass lesion on
imaging*
5.Presence of a local complication from acute pancreatitis which requires
pancreatogram
6.Regular use of opioid medication for abdominal pain for the past three months
7.Medication as the etiology for acute pancreatitis by physician assessment
8.TWEAK score >= 4
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03609944 |
| CCMO | NL68829.091.19 |