Effect of Negative-Pressure Drainage Versus Pancreatic Duct Stenting for Preventing Pancreatitis After Endoscopic Papillectomy for Duodenal Papillary Tumors: A Prospective, Multicenter, Randomized Controlled Trial
Phase: NA
Conditions: Ampulla of Vater Neoplasms, Ampullary Adenoma, Ampullary Carcinoma
Sponsor: Cui Xiaobing

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Clinical Study Protocol
Project Title：Effect of Negative-Pressure Drainage versus Pancreatic
Duct Stenting for Preventing Pancreatitis after Endoscopic Papillectomy
for Duodenal Papillary Tumors: A Prospective, Multicenter, Randomized
Controlled Trial
Protocol Version/Date：V4.0/2025-09-17
Lead Institution/Principal Investigator ：
Shenzhen Hospital of
Southern Medical University /Xiaobing Cui
Lead Institution Address ：
No. 13 Xinhu Road, Bao'an District,
Shenzhen, Guangdong, China
NCT Number ：NYSZYYEC2025K110R002

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Confidentiality Statement:
The information contained in this protocol is provided solely for
review by the investigators of this project, the ethics committee, and
relevant institutions. The copyright is owned by Shenzhen Hospital of
Southern Medical University. Without prior approval from Shenzhen
Hospital of Southern Medical University, it is strictly prohibited to
disclose any information herein to any third party unrelated to this study.

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Protocol Synopsis
Protocol Title
Effect of Negative-Pressure Drainage versus Pancreatic Duct
Stenting for Preventing Pancreatitis after Endoscopic Papillectomy
for Duodenal Papillary Tumors: A Prospective, Multicenter,
Randomized Controlled Trial
Sponsor
Shenzhen Hospital of Southern Medical University
Principal
Investigator
Wei Gong
Study Site(s)
and
Investigator(s)
Department of Gastroenterology, Shenzhen Hospital of Southern
Medical University — Wei Gong
Study
Population
Patients
aged
18–75
years
scheduled
to
undergo
endoscopic
papillectomy of the major duodenal papilla.
Study
Objectives
Primary objective
To
compare
the
effectiveness
of
negative-pressure
drainage
(experimental group) versus pancreatic duct stenting (control group)
in preventing pancreatitis after endoscopic papillectomy (EP).
Secondary objectives
(1) To compare the incidence of post-EP complications between the
two groups;
(2) To compare procedure duration and technical success rate
between the two groups;
(3) To compare length of hospital stay and total hospitalization costs
between the two groups;
(4) To compare complete (R0) resection rate and en bloc resection
rate of EP between the two groups;
(5) To compare the incidence of post-EP hyperamylasemia between
the two groups.
Study Groups
Experimental group: Negative-pressure drainage group—after EP,
endoscopic placement of a negative-pressure drainage tube in the
descending duodenum.
Control group: Pancreatic duct stent group—after EP, ERCP-guided
placement of a pancreatic duct stent.
Study Design
Prospective, multicenter, open-label, randomized controlled trial.
Study Duration
4 years
Sample Size
132 participants
Inclusion
Criteria
(1) Age 18–75 years
(2) Preoperative diagnosis of duodenal papillary adenoma or early
adenocarcinoma (≤T1a)

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(3) Planned endoscopic papillectomy
Exclusion
Criteria
(1) Preoperative diagnosis suggestive of adenocarcinoma ≥T1b;
(2) Preoperative imaging suggesting intraductal extension into the
pancreatic duct or bile duct ≥20 mm;
(3) Lesion diameter >40 mm, adjacent to a diverticulum, or other
conditions unsuitable for endoscopic therapy;
(4) Familial adenomatous polyposis (FAP);
(5) Severe cardiopulmonary disease unable to tolerate anesthesia and
endoscopic examination/treatment;
(6) Coagulation dysfunction;
(7) Pregnancy or lactation.
Efficacy
Analysis
Primary outcome: Incidence of pancreatitis after EP.
Secondary outcomes: Incidence of other post-EP complications;
length of hospital stay and total hospitalization costs; procedure
duration and technical success rate; complete (R0) resection rate and
en bloc resection rate; incidence of hyperamylasemia after EP.
Safety Analysis
Any adverse medical events occurring after the participant receives
treatment that are not included in the efficacy analyses.
Statistical
Analysis
Analysis sets
The Full Analysis Set (FAS), Per-Protocol Set (PPS), and Safety Set
(SS) will be used for statistical analyses.
FAS: All randomized participants, regardless of whether pancreatic
duct stenting or negative-pressure drainage tube placement is
ultimately completed or follow-up is completed.
PPS: A subset of the FAS who successfully receive negative-pressure
drainage tube placement or pancreatic duct stenting, complete
scheduled follow-up, have good compliance, and have no major
protocol violations or deviations.
SS: Participants who receive at least one study intervention
(negative-pressure drainage tube or pancreatic duct stent) and
subsequently undergo safety assessment.
Statistical analysis will be performed using SPSS version 27.
Follow-up
Participants with successful placement of a pancreatic duct stent or a
negative-pressure drainage tube after EP will be followed during
hospitalization and at 1 month post-procedure. During follow-up, any
participants with symptoms such as abdominal pain, bleeding, or
fever will return to the hospital within 24 hours for blood tests and
endoscopic evaluation to determine the cause of complications,

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which will be recorded in the CRF.
Statistical
Methods
Continuous data will be presented as mean ± standard deviation
(x̄±s). Between-group comparisons of continuous variables will use
the t test. Categorical variables will be compared using the
chi-square test and presented as percentages. P < 0.05 will be
considered statistically significant.
Expected
Timeline
4 years

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List of Abbreviations and Definitions
Abbreviation Definition
FAS
Full Analysis Set
PPS
Per-Protocol Set
SS
Safety Set
EP
Endoscopic Papillectomy
FAP
Familial
Adenomatous Polyposis
PD
Pancreaticoduodenectomy
AP
Acute Pancreatitis
ESGE
European Society of Gastrointestinal Endoscopy
ERCP
Endoscopic Retrograde Cholangiopancreatography
AE
Adverse Event
SAE
Serious Adverse Event

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Schedule of Study Procedures
Item
Screening
Day −3 to Day 0
Procedure Day
Intraoperative
During
hospitalization
Follow-up
1 month
post-procedure
Informed consent X
Demographics
X
Eligibility criteria X
Laboratory tests
X
X
X
Electrocardiogra
m
X
Endoscopic
examination
X
Blood pressure
and heart rate
X
X
X
X
Case report form
(CRF)
X
X
X
Adverse events
X
X
X
1. Background
Duodenal papillary tumors account for a relatively small proportion of all
gastrointestinal tumors, approximately 5%. However, with the widespread use of
upper gastrointestinal endoscopy and endoscopic retrograde
cholangiopancreatography (ERCP), the detection rate has been increasing [1,2].
Papillary adenomas may occur sporadically or in patients with familial adenomatous
polyposis (FAP), the latter being associated with mutations in the adenomatous
polyposis coli (APC) gene [3]. Adenoma is the most common benign papillary tumor;

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however, because it follows the adenoma-to-carcinoma sequence [4], the risk of
malignant transformation is as high as 25–85%. Therefore, it is regarded as a
premalignant lesion [3] that requires close surveillance and early resection to reduce
the risk of carcinogenesis.
Endoscopic papillectomy (EP) was first reported in Japan in 1983. In 1993,
Binmoeller et al. reported the first large cohort study [5], and EP has gradually
become an effective treatment for benign ampullary tumors. EP avoids the surgical
risks and postoperative complications associated with pancreaticoduodenectomy
(PD), and thus has been increasingly adopted in clinical practice. Nevertheless,
postoperative complications may still occur after EP, including pancreatitis,
post-procedural bleeding, perforation, and cholangitis, among which acute
pancreatitis (AP) is one of the most important risks [6]. To reduce the risk of
pancreatitis after EP, the European Society of Gastrointestinal Endoscopy (ESGE)
guideline recommends routine prophylactic pancreatic duct stenting after EP [7]. The
rationale is to prevent transient obstruction of the pancreatic orifice due to
postoperative edema and cautery effect, maintain normal pancreatic juice drainage,
and reduce pancreatic duct pressure load, thereby lowering the risk of pancreatitis.
However, a meta-analysis by Chandan et al. (2024) including 1,858 patients showed
similar overall incidences of AP between routine pancreatic duct stenting and no
stenting (11.9% vs 16.6%, respectively), without a statistically significant advantage
(p = 0.4) [8]. A systematic review and meta-analysis by Wang et al. (2019) also
suggested that pancreatic duct stenting may reduce the incidence of AP, but the
difference did not reach statistical significance (OR = 0.71; 95% CI: 0.36–1.40; p =
0.325) [9].
Furthermore, due to local tissue edema, clot obstruction, and bleeding after EP,
ERCP-guided pancreatic duct cannulation can be difficult even for experienced
endoscopists, leading to failure of pancreatic duct stent placement [10–13]. The
reported failure rate of pancreatic duct stent placement can be as high as 30% [14].

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When stent placement fails because of difficult cannulation after EP, the incidence of
pancreatitis may further increase. In addition, repeated cannulation attempts may
exacerbate mechanical irritation and inflammatory response of the pancreatic duct,
thereby increasing the risk of AP [15]. To address various difficulties in pancreatic
duct stent placement after EP, Desilets and colleagues proposed preoperative
pancreatic duct stenting strategies, such as preoperative dual sphincterotomy with
pancreatic duct stent placement [11], preoperative placement of an insulated plastic
pancreatic duct stent [16], and deep preoperative placement of a pancreatic duct stent
with postoperative suture adjustment of stent position [17]. These techniques have, to
some extent, improved post-procedural stent placement success and reduced
pancreatitis. However, they remain complicated and may be associated with stent
migration and post-procedural bleeding. Further optimization of postoperative
pancreatic juice drainage remains a key research focus.
To address this clinical problem, the present study innovatively proposes a
strategy of negative-pressure drainage in the descending duodenum as an alternative
to conventional pancreatic duct stenting, aiming to reduce the incidence of
pancreatitis and other complications after EP. In this approach, a negative-pressure
drainage tube is inserted through the nasal cavity and positioned on the anal side of
the papilla in the descending duodenum, with the distal end connected to a manually
compressed drainage bottle to maintain continuous negative-pressure suction and
promote effective drainage of pancreatic juice. This strategy not only avoids potential
mechanical injury caused by pancreatic duct cannulation but also simplifies
postoperative management. Theoretically, it may reduce the incidence of post-EP
pancreatitis, decrease procedural difficulty, and reduce related complications.
Recently, our center has applied negative-pressure suction in postoperative
management after EP in multiple cases. Preliminary clinical observations have shown
good recovery and no significant complications, supporting the feasibility of this
strategy and providing a practical foundation for subsequent systematic efficacy

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evaluation. However, to date, no systematic studies have been reported domestically
or internationally, and the clinical safety and effectiveness of this approach require
further validation. Therefore, we plan to conduct a multicenter randomized controlled
trial to evaluate the role of negative-pressure drainage versus pancreatic duct stenting
in reducing the risk of post-EP pancreatitis, optimizing perioperative management,
and reducing postoperative complications, thereby providing new evidence for
postoperative management after EP.
2. Study Objectives
2.1 Primary Objective
To compare the effectiveness of negative-pressure drainage (experimental group)
versus pancreatic duct stenting (control group) in preventing pancreatitis after
endoscopic papillectomy.
2.2 Secondary Objectives
(1) (1) To compare the incidence of post-EP complications between the two
groups;
(2) (2) To compare procedure duration and technical success rate between the
two groups;
(3) (3) To compare length of hospital stay and total hospitalization costs
between the two groups;
(4) (4) To compare complete (R0) resection rate and en bloc resection rate of
EP between the two groups;
(5) (5) To compare the incidence of post-EP hyperamylasemia between the two
groups.
3. Study Endpoints
3.1 Primary Endpoint
Incidence of pancreatitis after EP.
3.2 Secondary Endpoints
(1)(1) Incidence of other post-EP complications;
(2)(2) Procedure duration and technical success rate;

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(3)(3) Length of hospital stay and total hospitalization costs;
(4)(4) Complete (R0) resection rate and en bloc resection rate of EP;
(5)(5) Incidence of post-EP hyperamylasemia.
4. Study Design
This is a prospective, multicenter, open-label randomized controlled trial. The
study will be conducted in accordance with the CONSORT-AI guideline and the
Declaration of Helsinki. After written informed consent is obtained, patients meeting
the inclusion/exclusion criteria will be screened. Eligible participants will then be
randomized in a 1:1 ratio to the experimental group (negative-pressure drainage after
EP) or the control group (pancreatic duct stenting after EP). Participants will be
treated according to the assigned treatment regimen.
4.1 Randomization and Blinding
4.1.1 Randomization
In this study, patients meeting the inclusion/exclusion criteria will be assigned in
a 1:1 ratio to the experimental group (negative-pressure drainage group) and the
control group (pancreatic duct stent group). The random sequence will be generated
by concealed allocation at each participating center in blocks of 10 participants.
Randomization will be performed after the patient signs the informed consent form.
4.1.2 Blinding/Unblinding
Because the two interventions (placement of a negative-pressure drainage tube
versus placement of a pancreatic duct stent) differ inherently in their procedures (e.g.,
device configuration and visibility of an external drainage tube), blinding of the
operating endoscopist and participants is not feasible; therefore, the trial will be
conducted in an open-label manner. Imaging assessments and data analyses will be
performed by other medical professionals independent of the study.
5. Study Population
The study population consists of patients scheduled to undergo endoscopic
papillectomy of the duodenal papilla.
Patients
eligible for endoscopic resection
of
duodenal papillary
tumors

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according to the 2021 ESGE guideline, the 2015 ASGE guideline, etc.
5.2 Inclusion Criteria
(1) Age 18–75 years
(2)
Preoperative
diagnosis
of
duodenal
papillary
adenoma
or
early
adenocarcinoma (≤T1a)
(3) Planned endoscopic papillectomy
5.3 Exclusion Criteria
(1) Preoperative diagnosis suggestive of adenocarcinoma ≥T1b;
(2) Preoperative imaging suggesting intraductal extension into the pancreatic
duct or bile duct ≥20 mm;
(3) Lesion diameter >40 mm, adjacent to a diverticulum, or other conditions
unsuitable for endoscopic therapy;
(4) Familial adenomatous polyposis (FAP);
(5) Severe cardiopulmonary disease unable to tolerate anesthesia and
endoscopic examination/treatment;
(6) Coagulation dysfunction;
(7) Pregnancy or lactation.
5.4 Withdrawal Criteria
If a participant withdraws from the study for any reason, the reason must be
recorded, including but not limited to:
1) Withdrawal of informed consent;
2) Study termination by the sponsor;
3) Serious adverse events affecting the participant's ability to continue
participation;
4) Serious protocol violations/deviations;
5) Pregnancy;
6) Poor compliance;
7) Loss to follow-up;
8) The investigator and/or sponsor considers that the participant's medical

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condition may jeopardize participant safety or that continued participation may be
detrimental to the participant's health;
9) Death;
10) Other reasons.
5.5 Termination Criteria
If any of the following occurs, the principal investigator shall submit a termination
application to the ethics committee within 24 hours and terminate the study
immediately after approval.
(1) Abnormally increased incidence of postoperative complications (terminate
if any criterion is met)
1) Incidence of acute pancreatitis after the procedure in the control group >30%. 2)
Incidence of pancreatitis and/or other major complications (bleeding, perforation,
cholangitis, etc.) after the procedure in the experimental group is higher than that in
the control group. 3) Cumulative incidence of complications in the experimental
group exceeds the empirical threshold of 50%.
(2) Early termination based on interim analysis
After key follow-up has been completed for 66 participants, an independent
statistician will compare the incidence of pancreatitis after the procedure between
the two groups; if two-sided p < 0.05, an application for early termination may be
proposed.
(3) Major protocol deviations or defects
Major deviations, design defects, or operational errors that cannot be corrected by
revision or training and that seriously affect data integrity or participant safety.
(4) Requirements from regulatory or ethics bodies
Termination or suspension requested by the sponsor, ethics committee, or
regulatory authorities based on ethical, safety, or regulatory considerations.
6. Treatment Technique or Device
6.1 Study Devices
The negative-pressure drainage tube is made of flexible polymer material

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and is a transparent or semi-transparent white tubular device, with functions
including adjustable negative pressure, water/air infusion, and continuous suction.
Each product is supplied in sterile packaging, with the product name, model, batch
number, and expiration date clearly indicated on the package and label. In clinical
practice, similar devices such as a nasogastric tube, jejunal feeding tube, or
intestinal obstruction tube may be flexibly selected, without restriction to specific
brands or models.
The pancreatic duct stent is a routinely used stent product, mostly made of
silicone or medical-grade polymers, in a slender tubular shape, generally blue or
green in color. The packaging complies with national standards for medical devices,
and the label also indicates detailed product information. The brand, diameter, and
length of the pancreatic duct stent are not restricted and will be determined by the
operating endoscopist according to the patient's condition.
Supportive or rescue drugs and devices used during the study for prevention,
diagnosis, or treatment purposes, or as part of standard therapy for a diagnosed
disease, are considered non-investigational products.
After endoscopic papillectomy, participants in both groups will receive different
device-based interventions:
Negative-pressure drainage group: After EP, a negative-pressure drainage tube
will be inserted through the nasal cavity and positioned on the anal side of the
papilla in the descending duodenum. The distal end will be connected to a
manually compressed drainage bottle to maintain continuous negative-pressure
suction and promote effective drainage of pancreatic juice. Negative pressure
parameters will be adjusted according to the clinical condition to achieve timely
drainage of pancreatic juice and duodenal contents. If there are no obvious
complications after EP, the tube will be removed on postoperative day 3. If signs of
complications such as persistent massive bleeding or device-related perforation
occur intraoperatively, rescue intervention will be initiated immediately: a
pancreatic duct stent will be placed, and a negative-pressure drainage tube will also

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be placed to continue drainage. The timing of stent removal will follow the stent
removal procedure for the control group.
Pancreatic duct stent group: Conventional ERCP-guided pancreatic duct stent
placement will be performed. The pancreatic duct stent will be removed
endoscopically within 1 month post-procedure. All procedures will be performed
by experienced endoscopists according to standard operating procedures. If the
number of stent placement attempts is ≥3 or cumulative cannulation time
exceeds 15 min, placement will be considered a failure and will be immediately
converted to placement of a negative-pressure drainage tube; the tube position
and removal timing will follow the experimental group protocol.
Whether to place a biliary stent is not restricted in either group and will be
decided by the operating endoscopist based on the patient's condition.
If severe device-related adverse events occur during treatment (e.g., persistent
massive bleeding, severe pancreatitis, device-related perforation, or obvious
device malfunction), the relevant device should be discontinued immediately,
and the participant may be withdrawn from the study as appropriate to
ensure safety.
Information on all concomitant medications during the study (generic name,
indication, dose, and administration time, etc.) must be recorded in detail in
the case report form. Use of other investigational drugs from other clinical
trials is prohibited during the study.
All devices should be kept in intact packaging with clearly legible labels.
Devices must be stored in a temperature-controlled, dry environment away
from direct sunlight. Packaging integrity and expiration date should be
checked before use; devices with abnormalities must not be used and should
be reported promptly.
Devices will be managed centrally by designated personnel. Prior to
dispensing, packaging integrity and expiration date must be checked, and
dispensing records must be maintained. All operators must receive dedicated
training to ensure device use complies with standard operating procedures.

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At the end of the study or when safety concerns arise, unused or expired
investigational devices must be strictly collected and properly destroyed in
accordance with hospital and regulatory requirements. The collection process
must record the model, batch number, quantity, and date to ensure all devices
are managed in a standardized manner and do not enter the market.
7. Study Methods and Procedures
All participants must sign the informed consent form before screening; only
those who meet the inclusion criteria may enter the study.
Participants will be randomized into two groups: the negative-pressure drainage
group (experimental group) and the pancreatic duct stent group (control group).
All participants will undergo endoscopic papillectomy (EP), and during the
procedure, a negative-pressure drainage tube or a pancreatic duct stent will be placed
according to randomization. All participants will fast for 48 hours after the procedure
and receive intravenous fluids and nutritional support, as well as relevant medications
for prevention of infection, pancreatitis, and bleeding. After 48 hours, if imaging and
clinical indicators are normal, diet will be advanced gradually from clear liquids to a
soft diet, and parenteral nutrition will be continued as needed until oral intake is
restored.
During treatment, safety and efficacy endpoints will be assessed at predefined
time points, including incidence of pancreatitis after the procedure, EP-related
complications, length of hospital stay and costs, procedure duration, device technical
success rate, complete (R0) resection rate and en bloc resection rate, and incidence of
hyperamylasemia after EP.
Follow-up will be performed at 1 month after enrollment, and clinical status and
quality-of-life data will be collected. Treatment will continue until the participant
enters the follow-up period or meets any withdrawal criterion.
7.1 Screening Period
All participants must complete screening examinations before enrollment and
will be screened according to the inclusion/exclusion criteria.

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(1) Sign the informed consent form;
(2) Record demographic information: date of birth, sex, initials;
(3) Obtain detailed medical history and perform a physical examination (including
vital signs, height, weight, and systemic examination);
(4) Complete baseline laboratory tests: complete blood count, biochemical tests,
coagulation profile, urinalysis, stool routine test (fecal occult blood), etc.;
(5) As clinically indicated, perform relevant imaging examinations (e.g.,
abdominal ultrasound or CT) to exclude other indications;
(6) Eligible participants meeting criteria will enter the randomization stage.
7.2 Treatment Period
Eligible participants will undergo endoscopic papillectomy (EP) on the day of
the procedure, performed by senior endoscopists. After completion of EP, participants
will be allocated into the following two groups according to 1:1 randomization:
7.2.1 Control Group (Pancreatic Duct Stent Group, Figure A)
Immediately after EP, a prophylactic plastic pancreatic duct stent will be
placed under dual monitoring by endoscopy and fluoroscopy. The model and
length will be determined by the endoscopist based on preoperative imaging
assessment. Placement of a biliary stent is not restricted.
If the number of stent placement attempts is ≥3 or cumulative cannulation time
exceeds 15 min, placement will be considered a failure and will be immediately
converted to placement of a negative-pressure drainage tube; the tube position
will follow the experimental group protocol.
For participants with successful stent placement, the stent will be removed
endoscopically within 30 days after the procedure; for those converted to
negative-pressure drainage tube placement, the tube will be removed after
assessment at 72 h post-procedure confirming no complications.
7.2.2 Experimental Group (Negative-Pressure Drainage Group, Figure B)
After EP, a negative-pressure drainage tube will be inserted through the nasal
cavity and its tip positioned on the anal side of the papilla in the descending
duodenum. The distal end will then be connected to a manually compressed
drainage bottle to continuously drain pancreatic juice and duodenal contents.
If signs of complications such as persistent massive bleeding or device-related

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perforation
occur
intraoperatively, rescue
intervention
will
be initiated
immediately: a pancreatic duct stent will be placed, and a negative-pressure
drainage tube will also be placed to continue drainage.
For participants with successful placement of the negative-pressure drainage
tube, the tube will be removed after assessment at 72 h post-procedure
confirming no significant complications; for those converted to pancreatic duct
stent placement, stent removal will follow the control group procedure.
Figure A. Placement of a conventional pancreatic duct stent and biliary stentFigure B. Placement of a
negative-pressure drainage tube
7.3 Follow-up Period
(1) After completion of treatment, all participants will enter the follow-up period,
including
follow-up
during
postoperative
hospitalization
and
at
1
month
post-procedure.
(2) Record clinical status and complications during hospitalization and within 1
month after the procedure in both groups; collect relevant laboratory tests (e.g.,
serum amylase, lipase, CRP, liver function, etc.). In the control group (pancreatic
duct stent group), the stent will be removed endoscopically within 1 month after the
procedure, and the removal process and related complications will be recorded. In the
experimental group (negative-pressure drainage group), the drainage tube will be
removed on postoperative day 3 if there are no complications, and drainage tube
function, displacement, obstruction, etc. will be recorded.
(3) Follow-up data will be used for statistical analyses to compare differences in
efficacy and safety endpoints between negative-pressure drainage and pancreatic duct
stenting;
(4) Based on follow-up results, investigators will further evaluate the long-term
benefits and risks of the two strategies, providing scientific evidence to optimize
postoperative management after EP.

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8. Outcome Measures
8.1 Efficacy Assessments
- Incidence of pancreatitis after EP in the negative-pressure drainage group vs the
pancreatic duct stent group
- Incidence of other complications
- Length of hospital stay and total hospitalization costs
- Procedure duration and technical success rate
- Complete (R0) resection rate and en bloc resection rate of EP
- Incidence of hyperamylasemia after EP
1)
Acute pancreatitis (AP): defined according to the revised 2012 Atlanta
Classification [18], requiring at least 2 of the following 3 criteria: (1) persistent
upper abdominal pain; (2) serum amylase or lipase at least three times the upper
limit of normal; (3) characteristic findings of AP on computed tomography.
2)
Severity of AP: Based on the revised 2012 Atlanta Classification, AP is
categorized as mild, moderately severe, or severe according to the presence and
duration of organ failure and local or systemic complications.
3)
Hyperamylasemia: postoperative serum amylase above the upper limit of normal
without clinical symptoms, and imaging excludes acute pancreatitis.
4)
Other post-EP complications: includes bleeding, perforation, and cholangitis
after EP.
a)
Post-EP bleeding: hematemesis, melena, or hematochezia after EP, with a
decrease in hemoglobin ≥2 g/dL compared with baseline, or requiring blood
transfusion or endoscopic hemostasis.
b)
Post-EP perforation: a perforation identified during or after EP, or imaging
evidence of free air.
c)
Post-EP cholangitis:
postoperative
fever
with
elevated
inflammatory
markers and imaging evidence of bile duct dilation or infection, requiring
antibiotic therapy.
d)
Incidence of post-EP complications: the proportion of participants who

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develop any of the above complications.
5)
Complete
(R0)
resection
rate:
the
proportion
of
participants
with
histopathologically negative horizontal and vertical margins.
6)
En bloc resection rate: the proportion of participants whose lesion is removed in
a single piece.
7)
Procedure duration: time from insertion of the endoscope to completion of the
procedure.
8)
Technical success rate: the proportion of participants in whom the assigned
intervention (pancreatic duct stent placement or negative-pressure drainage tube
placement) is successfully completed.
9)
Length of hospital stay: the total number of days hospitalized.
10) Total hospitalization costs: the total cost incurred during hospitalization.
8.2 Safety Assessments
Safety assessments include relevant parameters, methods and time points of
evaluation, and procedures for recording and reporting adverse events (AEs) and
concomitant diseases, including reporting procedures as well as follow-up forms and
duration after AE occurrence.
9. Safety Monitoring, Reporting, and Medical Management
9.1 Definition of Adverse Events (AEs)
An adverse event (AE) refers to any unfavorable medical occurrence in a patient
or participant after receiving a study device, which does not necessarily have a causal
relationship with the treatment. Therefore, an AE may be any unfavorable sign
(including abnormal laboratory findings), symptom, or disease temporally associated
with use of the device, whether or not considered related to the investigational device.
AEs include serious adverse events (SAEs) and non-serious adverse events.
9.2 Definition of Serious Adverse Events (SAEs)
A serious adverse event (SAE) is any adverse event that results in death; is
life-threatening; requires inpatient hospitalization or prolongation of existing
hospitalization; results in persistent or significant disability/incapacity; or causes a

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congenital anomaly/birth defect. Additionally, other important medical events that
may not result in death or hospitalization but may jeopardize the participant or
require intervention to prevent one of the outcomes listed above are also considered
SAEs.
9.2.1 Death
Death refers to a participant's death from any cause during the study.
9.2.2 Life-threatening event
A life-threatening event refers to an event in which the participant was at
immediate risk of death at the time of the event.
9.2.3 Hospitalization or prolongation of hospitalization
Hospitalization refers to admission to a hospital for treatment or observation, or
prolongation of existing hospitalization due to an adverse event.
9.3 Recording, Collection, Reporting, and Management of Adverse Events
9.3.1 Collection, Reporting, and Management of AEs
From signing informed consent until completion of follow-up (1 month after the
procedure), all adverse events occurring in participants must be recorded and
evaluated.
All adverse events should be documented in the case report form, including time
of occurrence, severity, duration, outcome, and measures taken. The severity of AEs
will be graded according to the Common Terminology Criteria for Adverse Events
(CTCAE) v5.0. Investigators should determine the causal relationship between the
AE and the study intervention.
9.3.2 Management and Handling of AEs
9.3.3 Collection and Reporting of SAEs
All serious adverse events (SAEs) must be reported to the sponsor and the ethics
committee within 24 hours, and relevant information should be recorded in
detail.
SAE reports should include the participant's identification code, a description of
the event, time of onset, severity, outcome, treatment measures, and the investigator's

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assessment of causality.
9.3.4 Treatment of AEs/SAEs
Participants experiencing AEs/SAEs should receive appropriate medical
treatment according to clinical needs. Study interventions may be discontinued,
modified, or additional treatments may be provided as necessary to ensure participant
safety.
9.3.5 Pregnancy
If pregnancy occurs during the study, the participant should be withdrawn
immediately and the pregnancy should be reported as an SAE within 24 hours. The
pregnancy outcome should be followed until completion.
All clinical laboratory tests will be performed by the clinical laboratory of the
participating hospital and will comply with relevant laws and regulations.
Quality Control and Assurance of Laboratory Testing
9.3.6
9.3.5 Other Responsibilities of the Investigator During Follow-up of Serious Adverse Events
Based on clinical judgment, the investigator should conduct appropriate evaluations and
provide necessary treatment for the SAE, including (but not limited to) clinically indicated
laboratory tests and physical examinations. Any results of such evaluations, or any newly
available or updated information related to the SAE, must be submitted as follow-up reports; the
timelines and procedures for follow-up reporting are the same as those for the initial SAE report.
9.3.6
10. Criteria for Trial Termination/Suspension
The sponsor has the right to terminate/suspend this trial. Before terminating or
suspending a clinical trial, the sponsor shall notify the investigators, the ethics
committee, and the medical device clinical trial management department, and state
the reasons. After early termination/suspension, restarting the study requires ethics
committee approval.
Termination/Suspension as required by the Ethics Committee.
11. Criteria for Completion of the Clinical Trial

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The trial will end when all participants meet the following conditions:
1) All participants have completed at least 1-month follow-up;
2) Or all participants have died, are lost to follow-up, or have withdrawn
informed consent.
12. Data Management
12.1 Data Management
1) Investigators must ensure that data are truthful, complete, and accurate;
2) Any correction to trial records must be made by striking through the original
entry, writing the corrected data in the margin, stating the reason, and signed and
dated by the investigator; erasing or overwriting the original record is not allowed;
3) Laboratory test items must be complete.
12.2 Data Recording and Document Retention
Subject data on the case report form shall be recorded using subject codes;
subjects may be identified only by their subject code or initials.
Clinical data will be stored by data management personnel on an encrypted
laboratory computer. After data are confirmed to be free of queries, all parties will
sign the database lock request form, and the data manager will lock the database.
After database lock, the data manager will export the analysis dataset and provide it
to the statistician for statistical analysis. Locked data cannot be edited. Any issues
identified after database lock, once confirmed, may be corrected within the statistical
analysis programs.
13. Statistical Analysis
13.1 Sample Size Calculation
This study is a prospective randomized controlled trial (RCT) designed to
evaluate the effectiveness of negative-pressure drainage in preventing pancreatitis
after endoscopic papillectomy (EP). According to the study by Jiang et al., the
incidence of acute pancreatitis after EP in the pancreatic duct stent group was 31%.
Considering that the characteristics of our study population and real-world clinical
practice are similar, an event rate of 30% is used as the control-group event rate for
sample size estimation. The expected event rate in the experimental group

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(negative-pressure drainage group) is 10%. Sample size parameters were set as
follows: significance level α = 0.05 (two-sided), power 1−β = 80%, and allocation
ratio R = 1 (i.e., 1:1 randomization). Using PASS 15 software, the results indicated
that 62 participants per group are required. Considering a 5% dropout rate in practice,
the final total sample size is 132 participants, i.e., 66 participants per group.
13.2 Statistical Analysis
The significance level is set at α = 0.05 (two-sided), and all hypothesis tests are
two-sided. Continuous data will be described as mean ± standard deviation
(x̄±s). Between-group comparisons of continuous variables will use the t test.
Categorical variables will be compared using the chi-square test and described
as percentages. P < 0.05 will be considered statistically significant.
To improve study efficiency and ensure participant safety, one interim analysis
is planned. After enrollment of 50% of the sample size (i.e., 33 participants per
group, 66 in total), a preliminary evaluation of the primary endpoint event
(postoperative pancreatitis) will be performed. The interim analysis will use the
O'Brien–Fleming boundary method to control the overall type I error rate (α =
0.05), with a stringent significance threshold set for the interim stage (p < 0.0054)
to ensure reliability of statistical conclusions. If the interim analysis demonstrates a
significant difference between groups for the primary endpoint and meets the
prespecified statistical boundary, the study team will consider early termination of
the trial and submit the interim analysis report and recommendation for termination
to the ethics committee.
In addition, considering the clinical context and potential practical advantages
of the intervention, secondary endpoints will be evaluated concurrently at the
interim analysis, including incidence of hyperamylasemia, cannulation success rate,
procedure duration, length of hospital stay, and hospitalization costs. If the
experimental group does not show a statistically significant difference in the
primary endpoint but demonstrates clear clinical advantages in these secondary
endpoints, this may also serve as a basis for early termination. The study team will

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comprehensively assess efficacy, safety, procedural feasibility, and patient benefit,
and will decide whether to end the trial early after thorough deliberation.
The interim analysis will be performed by an independent statistician, and the
analysis process will remain blinded to avoid bias affecting subsequent enrollment
and interventions. All interim analysis results and decision recommendations will
be submitted to the ethics committee for review. The interim analysis design and
any potential early termination are premised on safeguarding participants’ rights
and interests. All decisions will be made strictly based on statistical results and
ethical principles to ensure the scientific rigor and fairness of the study.
13.3 Definition and Selection of Analysis Sets
The Full Analysis Set (FAS) includes all enrolled participants who receive at
least one study device and have at least one valid efficacy assessment.
The Safety Set (SS) includes all enrolled participants who receive at least one
study device and have at least one safety assessment.
The Per-Protocol Set (PPS) includes all cases in the FAS who complete the
protocol-specified treatment without major protocol violations.
13.4 Statistical Methods
Analyses will include participant disposition, demographic characteristics and
baseline analyses, feasibility and safety analyses, and efficacy analyses.
13.5 Statistical Software and General Requirements
All statistical analyses will be performed using SPSS v27 or other statistical
software.
Continuous variables will be described using mean, standard deviation,
median, minimum, and maximum.
Categorical variables will be described using frequencies and percentages.
For this study, the main endpoints (efficacy, postoperative outcomes, and
complication rates) will be analyzed using the chi-square test.
14. Trial Management
14.1 Compliance with Good Clinical Practice (GCP)

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Trial management organization and implementation of medical device clinical
trial management requirements:
1) Both the medical device trial applicant and the investigators shall
implement a quality control and quality assurance system for the clinical trial
using standard operating procedures (SOPs);
2) Source documents must comply with China’s GCP requirements;
3) Laboratory test results must be accurate and reliable;
4) All observations and findings must be verified to ensure data reliability;
5)
Establish
a
complete
trial
organizational
structure
and
clarify
responsibilities of personnel at all levels;
6) The principal investigator will be responsible for overall quality control and
for implementing responsibilities at all levels;
7) The principal investigator will be responsible for designing the protocol and
the informed consent form and implementing the trial after obtaining the
consent of the medical device trial applicant. After the trial is completed, the
principal investigator will prepare the final study report;
8) Designated investigators will be responsible for developing detailed trial
implementation procedures and SOPs for use during the trial;
9) Before trial initiation, the study team will organize all participants to study
the protocol; all trial personnel must receive GCP training;
10) Physicians and nurses participating in the trial must strictly comply with
the protocol requirements and procedures and must not modify them without
authorization;
11) Designated statisticians will be responsible for comprehensive statistical
processing of the data.
14.2 Protection of Participant Privacy
All data collected during the trial will be entered into a computer system for
confidential storage and analysis. When necessary, relevant institutions may audit the
records to verify the truthfulness, accuracy, and completeness of the data. Trial results

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may be published in academic journals; however, participants’ names will not be
disclosed, and participant privacy will be protected.
Additional preventive measures will be taken to ensure confidentiality of
documents and to prevent identification of participants based on genetic data.
However, under special circumstances, certain individuals may access a participant’s
genetic data and personal identification code. For example, in a medical emergency,
the sponsor, its representative physicians, or investigators may know the participant
identification code and have access to that participant’s genetic data. In addition,
relevant regulatory authorities may require access to related documents.
14.3 Problems Occurring During the Trial and Mitigation Measures
1) Protocol amendments: After ethics committee approval, if amendments are
needed, a 'Protocol Amendment Explanation' must be prepared and signed by the
principal investigator. Amendments may be made only after agreement between the
investigators and the device registration applicant;
2) After protocol amendment, it must be submitted to and approved by the ethics
committee before implementation;
3) No trial personnel may deviate from the protocol. If a deviation occurs, an
explanation must be written and the device registration applicant notified, who has
the right to decide whether the trial should continue;
4) If a participant has a minor protocol deviation, the research staff should notify
the device registration applicant promptly and jointly discuss how to handle the
deviation and whether the participant should be withdrawn. Minor deviations that do
not affect participant safety or protocol integrity are considered minor protocol
deviations;
5) Any adverse event (AE) or serious adverse event (SAE) occurring during the
trial will be reported and managed in accordance with this protocol and SOPs.
14.4 Quality Control and Quality Assurance
14.4.1 Quality Assurance
The sponsor, and any collaborating entities entrusted by the sponsor with all or

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part of the responsibilities and tasks related to this study (including CROs, SMOs,
statistical units, clinical centers, etc.), shall each establish their own quality assurance
systems, fulfill their respective responsibilities, and strictly adhere to the protocol,
using appropriate SOPs to ensure implementation of the clinical trial quality control
and quality assurance system.
14.4.2 Quality Assurance During the Clinical Trial Process
Before trial initiation, investigators should receive training on the protocol to
ensure that the study staff have a thorough understanding of the protocol and the
specific meaning of each endpoint. Quality control personnel should verify the basic
conditions for conducting the clinical trial to ensure that the trial conditions meet
protocol requirements. During the trial, investigators should perform clinical
procedures in accordance with the institution’s SOPs and protocol requirements, and
record data truthfully, promptly, completely, and in a standardized manner. Quality
control personnel will perform quality checks of the trial process and relevant source
records. After the trial is completed, the study site will organize the project
documents, which will be verified by quality control personnel and then archived for
retention. The quality assurance department of the clinical research unit will conduct
feasibility audits of the trials conducted. When noncompliance is identified,
investigators and the responsible person at the site will be promptly notified to
correct it, and the correction will be tracked.
14.5 Expected Timeline and Study Completion Date
June 2025 to December 2027: Complete patient recruitment, randomization,
treatment, and follow-up.
January 2028 to July 2028: Data statistical analysis.
August 2028 to June 2029: Manuscript preparation.
14.6 Sponsor Responsibilities
The sponsor is responsible for initiating, applying for, and organizing this
clinical trial and providing trial funding. In accordance with regulations such as the
Chinese regulations on medical device clinical trial management and medical device

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registration administration, the sponsor will submit the clinical trial application to the
China Food and Drug Administration (CFDA), and may also entrust a contract
research organization (CRO) to perform certain work and tasks in the clinical trial.
The sponsor selects the clinical trial institutions and investigators, and confirms
their qualifications and conditions to ensure completion of the trial.
The sponsor provides the investigational devices to investigators and shall
establish a management system and record-keeping system for investigational
devices.
14.6.1 Investigator Responsibilities
This clinical study will be conducted in accordance with the ethical, moral, and
scientific principles set forth in the Declaration of Helsinki and China’s GCP, as well
as the protocol design and requirements.
Investigators are responsible for making medical decisions related to the clinical
trial and ensuring that participants receive timely treatment when AEs occur during
the trial. Investigators should be familiar with the procedures and requirements for
reporting SAEs and record and report such events as required.
14.6.2 Sponsor’s Method for Publication of Study Data
The sponsor has exclusive rights to the study data. Unless written consent is
obtained from the sponsor, no individual publication should be made before
completion of the final report of the multicenter study. The sponsor has the final
decision on manuscripts and publications.
15. Trial-Related Ethics
15.1 Ethics Committee
Before trial initiation, investigators must submit the investigator’s brochure,
protocol, informed consent form, investigational device inspection report (as
applicable), and any other information provided to participants to the ethics
committee for review and approval. Any amendments to the protocol must also be
approved by the ethics committee.
15.2 Informed Consent

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Qualified investigators must explain in detail to each participant, as part of the
informed consent process, the nature and purpose of the trial, procedures, expected
duration, potential risks and benefits, and any possible discomfort. Each participant
must understand that participation is voluntary and that he/she may withdraw from
the trial and withdraw informed consent at any time without affecting subsequent
treatment or the relationship with the treating physician.
The informed consent form should be written in a standard format and, as far as
possible, use non-technical language. Each informed consent form must include all of
the above information and a statement of voluntariness. The informed consent form
must be submitted to the ethics committee for approval.
After explaining the basic content of the trial and confirming that each
prospective participant understands the purpose of the trial, the investigator should
ask each prospective participant to sign and date the informed consent form. The
participant should read and consider the statement before signing and dating, and
should receive a copy of the signed informed consent form for retention. Without
obtaining informed consent and a signed informed consent form, the participant
cannot be enrolled in the trial.
15.3 Other
When a participant is unable to independently participate in the informed
consent process, a reliable impartial witness/legal representative must be present
throughout the informed consent process. Selection of the impartial witness/legal
representative must not infringe upon the participant’s confidentiality rights. After the
participant provides oral consent, the impartial witness/legal representative should
sign and date the informed consent form to certify that the information is accurate.
16. References
[1]Han J, Kim M H. Endoscopic papillectomy for adenomas of the major duodenal
papilla (with video)[J]. Gastrointestinal Endoscopy, 2006, 63(2): 292-301.
[2]Scarpa A, Capelli P, Zamboni G, et al. Neoplasia of the ampulla of vater. Ki-ras
and p53 mutations[J]. American Journal of Pathology, 1993, 142(4): 1163-1172.

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[3]Ardengh J C, Kemp R, Lima-Filho É R, et al. Endoscopic papillectomy: the limits
of the indication, technique and results[J]. World Journal of Gastrointestinal
Endoscopy, 2015, 7(10): 987-994.
[4]Espinel J, Pinedo E, Ojeda V, et al. Endoscopic ampullectomy: a technical
review[J]. Rev Esp Enferm Dig.
[5]Binmoeller K F, Boaventura S, Ramsperger K, et al. Endoscopic snare excision of
benign adenomas of the papilla of vater[J]. Gastrointestinal Endoscopy, 1993, 39(2):
127-131.
[6]Chang W I, Min Y W, Yun H S, et al. Prophylactic pancreatic stent placement for
endoscopic duodenal ampullectomy: a single-center retrospective study[J]. Gut and
Liver, 2014, 8(3): 306-312.
[7]Vanbiervliet G, Strijker M, Arvanitakis M, et al. Endoscopic management of
ampullary
tumors:
european
society
of
gastrointestinal
endoscopy
(ESGE)
guideline[J]. Endoscopy, 2021, 53(04): 429-448.
[8]Chandan S, Canakis A, Deliwala S, et al. Prophylactic pancreatic duct stenting to
reduce the risk of post-ampullectomy pancreatitis: a comprehensive review and
meta-analysis of 1858 patients[J]. Surgical Endoscopy, 2024, 38(9): 4798-4813.
[9]Wang Y, Qi M, Hao Y, et al. The efficacy of prophylactic pancreatic stents against
complications of post-endoscopic papillectomy or endoscopic ampullectomy: a
systematic review and meta-analysis[J]. Therapeutic Advances in Gastroenterology,
2019, 12: 1756284819855342.
[10]Lee T Y, Cheon Y K, Shim C S, et al. Endoscopic wire‐guided papillectomy
versus conventional papillectomy for ampullary tumors: a prospective comparative
pilot study[J]. Journal of Gastroenterology and Hepatology, 2016, 31(4): 897-902.
[11]Desilets D J, Dy R M, Ku P M, et al. Endoscopic management of tumors of the
major duodenal papilla: refined techniques to improve outcome and avoid
complications[J]. Gastrointestinal Endoscopy, 2001, 54(2): 202-208.
[12]Ru N, Chai N, Zhang B, et al. Impact of pancreatic and biliary stent on
post-endoscopic papillectomy complications: a single-center retrospective study[J].

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Chinese Medical Journal, 2024, 137(17): 2111-2118.
[13]Kim S H, Moon J H, Choi H J, et al. Usefulness of pancreatic duct wire-guided
endoscopic papillectomy for ampullary adenoma for preventing post-procedure
pancreatitis[J]. Endoscopy, 2013, 45(10): 838-841.
[14]Gambitta P, Aseni P, Villa F, et al. Safety of endoscopic snare ampullectomy for
adenomatous ampullary lesions: focus on pancreatic stent placement to prevent
pancreatitis[J]. Surgical Laparoscopy, Endoscopy and Percutaneous Techniques, 2021,
31(4): 462.
[15]Taglieri E, Micelli-Neto O, Bonin E A, 等. Analysis of risk factors associated
with acute pancreatitis after endoscopic papillectomy[J]. Scientific Reports, 2020, 10:
4132.
[16]Hwang J C, Kim J H, Lim S G, et al. Endoscopic resection of ampullary
adenoma after a new insulated plastic pancreatic stent placement: a pilot study[J].
Journal of Gastroenterology and Hepatology, 2010, 25(8): 1381-1385.
[17]Nakahara K, Okuse C, Suetani K, et al. A novel endoscopic papillectomy after a
pancreatic stent placement above the pancreatic duct orifice: inside pancreatic
stenting papillectomy[J]. Journal of clinical gastroenterology, 2014, 48(9): 796-800.

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Participant Signature Page
Informed Consent Statement:
I have been informed of the purpose, background, procedures, risks, and
potential benefits of this study. I have had sufficient time and opportunity to ask
questions, and I am satisfied with the answers provided.
I have also been informed whom to contact if I have questions, wish to report
difficulties or concerns, have suggestions about the study, want further information,
or wish to offer assistance to the study. I understand that I may choose not to
participate in this study, or may withdraw from the study at any time during the
study without giving any reason. In addition, the investigators have not used
deception, inducement, coercion, or other means to force me to agree to participate
in the study.
I understand that if my condition worsens,
or I experience a serious adverse reaction, or my study physician believes that
continuing participation is not in my best interest, he/she may decide to withdraw
me from the study. The sponsor or regulatory authorities may also terminate the
study during the study period without obtaining my consent. If this occurs, the
physician will notify me in a timely manner and the study physician will discuss
my other options with me.
I have read this informed consent form and agree to participate in this study. I
will receive a copy of this informed consent form bearing the signatures of both
myself and the investigator.
Participant signature:
Date:

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Contact phone number:
Legal representative signature:
Relationship:
Date:
Contact phone number:
(Note: If the participant lacks or has limited capacity to act, such as inclusion of
vulnerable groups with mental disorders or impaired consciousness, the legal
representative must sign in the space below.)
Independent witness signature:
Date:
Contact phone number:
(Note: An independent witness signature is required only when the participant may
have decision-making capacity but is unable to read the text (e.g., illiterate, visually
impaired). When a witness is present, the investigator should, if possible, retain video
documentation as evidence of informed consent.)
I have accurately explained this document to the participant, he/she has read
this informed consent form accurately, and I confirm that the participant had the
opportunity to ask questions and voluntarily agreed.
Investigator signature:
Date：
Contact phone number：