Plain English Summary
Background and study aims
Acute biliary pancreatitis is inflammation of the pancreas caused by obstruction of the pancreatic duct. Relieving the obstruction early with an operation called endoscopic retrograde cholangiography (ERC) with endoscopic sphincterotomy (ES) may be beneficial, especially if this condition is persistent. The aim of this study is to investigate whether early detection of common bile duct obstruction followed by direct treatment of such an obstruction with ERC plus ES, reduces complications and/or the number of deaths in patients with acute biliary pancreatitis.
Who can participate?
Adult patients with acute biliary pancreatitis
What does the study involve?
Participants are treated with early EUS (endoscopic ultrasound) (within 24 hours of admission to hospital) followed by direct ERC plus ES, if they have sludge and/or gallstones in their common bile duct.
What are the possible benefits and risks of participating?
Patients with sludge and/or gallstones in the common bile duct may benefit from undergoing ERC plus ES, as early clearance of the obstruction can be beneficial. In patients without biliary obstruction, unnecessary ERC plus ES can be prevented. The potential risk of participating is that the ERC plus ES procedure may lead to complications in a minority of patients; however, there are several safety procedures and evaluation moments to guarantee the patients’ safety throughout the study. These complications include bleeding, bowel perforation, cholangitis and aspiration pneumonia; however, these complications occur in around 1% of cases.
Where is the study run from?
Erasmus Medical Center (The Netherlands) and 18 participating centres in the Netherlands
When is the study starting and how long is it expected to run for?
June 2017 to September 2019
Who is funding the study?
Erasmus Medical Center (The Netherlands)
Who is the main contact?
Prof. M.J. Bruno
m.bruno@erasmusmc.nl
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
MEC-2012-357
Study information
Scientific title
EUS-guided early ERC with sphincterotomy in predicted severe biliary pancreatitis: a prospective, multicenter cohort study with a historic comparison
Acronym
APEC-2
Study hypothesis
We hypothesise that endoscopic ultrasonography (EUS)-guided early endoscopic retrograde
cholangiography (ERC) with sphincterotomy improves the outcome of patients with acute biliary
pancreatitis without cholangitis, in whom the disease course is predicted to be severe.
Ethics approval
Erasmus Medical Center Rotterdam Ethics Committee, 27/06/2017 ref: MEC-2012-357
Study design
Interventional prospective multi-centre non-randomised cohort study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Patient information can be found at https://pancreatitis.nl/studies/apec
Condition
Acute biliary pancreatitis
Intervention
The study will be performed by the Dutch Pancreatitis Study Group. A total of 78 evaluable patients will be included in 18 participating centers. This group will receive early (<24 hours of admission) endoscopic ultrasound, followed by direct endoscopic retrograde cholangiography (ERC) with sphincterotomy if they have sludge or gallstones in the common bile duct. This will be compared with a historic cohort (the superior group of the APEC trial (ISRCTN97372133)). If the APEC trial shows no difference between the two groups, the conservative group or the early ERC with sphincterotomy group, a comparison will be made between the EUS group and the conservative group.
There will be a 6 month follow-up period, which will involve participants filling in questionnaires 1, 3 and 6 months after inclusion. 3 months after inclusion there will be a follow-up visit at the outpatient clinic to assess liver and pancreatic function.
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measure
Composite of severe morbidity and mortality occurring until 6 months after inclusion. Severe morbidity is defined as the occurrence of persistent single organ failure, necrotizing pancreatitis, bacteremia, cholangitis, pneumonia or exocrine or endocrine pancreatic insufficiency. After patient inclusion is completed and after the last patient has completed the 6 month follow-up, an adjudication committee consisting of 4 gastroenterologists, 2 surgeons and 1 radiologist will assess all potential endpoints (i.e. mortality and severe complications) and decide whether these concord with definitions of the primary endpoints. Using primary source data, each member of the committee will individually assess the potential endpoints. Disagreements will be resolved at a plenary consensus meeting.
Secondary outcome measures
The following are assessed at 6 month follow-up. For the secondary endpoints three sources of data are used: clinical record forms that are filled out by the treating physicians, primary source data and questionnaires filled out by the patients at 1,3 and 6 month follow-up.
1. Individual components of the primary endpoint
2. Length of hospital stay
3. Need for of new intensive care admission
4. Length of intensive care stay
5. Respiratory complications
6. Endoscopic retrograde cholangiography (ERC) related complications
7. Number of endoscopic, radiological and operative (re-)interventions
8. Readmission for biliary events
9. Difficulty of cholecystectomy
10. Economical evaluation
Overall trial start date
27/06/2017
Overall trial end date
01/09/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Acute biliary pancreatitis
2. Predicted severe disease course
3. EUS and ERC with sphincterotomy can be performed within 24 hours after admission
4. Aged 18 years or older
5. Written informed consent
6. In case of a previous episode of necrotizing pancreatitis, patient should be fully recovered
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
78 evaluable patients
Participant exclusion criteria
1. Cholangitis
2. Acute pancreatitis due to other causes such as alcohol abuse, metabolic causes, medication, trauma, etc.
3. Previous (precut) sphincterotomy
4. Chronic pancreatitis
5. International Normalised Ratio (INR) that cannot be corrected with co-fact or fresh frozen plasma below 1.5
6. Pregnancy
Recruitment start date
15/08/2017
Recruitment end date
01/03/2019
Locations
Countries of recruitment
Netherlands
Trial participating centre
Erasmus Medical Center
Doctor Molewaterplein 40
Rotterdam
3015 GD
Netherlands
Trial participating centre
Albert Schweitzer Hospital
Albert Schweitzerplaats 25
Dordrecht
3318 AT
Netherlands
Trial participating centre
Amphia Hospital
Molengracht 21
Breda
4818 CK
Netherlands
Trial participating centre
Amsterdam University Medical Centers location AMC
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
Trial participating centre
Amsterdam University Medical Centers location VUmc
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
Trial participating centre
Elisabeth Tweesteden Hospital
Doctor Deelenlaan 5
Tilburg
5042 AD
Netherlands
Trial participating centre
Erasmus Medical Center
Doctor Molewaterplein 40
Rotterdam
3015 GD
Netherlands
Trial participating centre
Franciscus Gasthuis
Kleiweg 500
Rotterdam
3045 PM
Netherlands
Trial participating centre
Gelre Hospital
Albert Schweitzerlaan 31
Apeldoorn
7334 DZ
Netherlands
Trial participating centre
Isala Klinieken
Dokter van Heesweg 2
Zwolle
8025 AB
Netherlands
Trial participating centre
Martini Hospital
Van Swietenplein 1
Groningen
9728 NT
Netherlands
Trial participating centre
Meander Medical Center
Maatweg 3
Amersfoort
Hoogland
3813 TZ
Netherlands
Trial participating centre
Medisch Spectrum Twente
Koningsplein 1
Enschede
7512 KZ
Netherlands
Trial participating centre
Onze Lieve Vrouwe Gasthuis
Oosterpark 9
Amsterdam
1091 AC
Netherlands
Trial participating centre
Radboud University Medical Center
Geert Grooteplein Zuid 10
Nijmegen
6525 GA
Netherlands
Trial participating centre
Reinier de Graaf Hospital
Reinier de Graafweg 5
Delft
2625 AD
Netherlands
Trial participating centre
Spaarne Gasthuis
Boerhaavelaan 22
Haarlem
2035 RC
Netherlands
Trial participating centre
St Antonius Hospital
Koekoekslaan 1
Nieuwegein
3435 CM
Netherlands
Trial participating centre
Gelderse vallei Hospital
Willy Brandtlaan 10
Ede
6716 RP
Netherlands
Sponsor information
Organisation
Erasmus Medical Center
Sponsor details
Doctor Molewaterplein 40
Rotterdam
3015 GD
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Not defined
Funder name
Investigator initiated and funded
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal
IPD sharing statement:
All requests for access to data generated as a result of this study should be send to M.J. Bruno (m.bruno@erasmusmc.nl) and will be reviewed by the board of the Dutch Pancreatitis Study Group to ensure scientific integrity and data protection.
Intention to publish date
01/03/2020
Participant level data
Available on request
Basic results (scientific)
Publication list