Condition category
Digestive System
Date applied
28/08/2018
Date assigned
10/09/2018
Last edited
10/09/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

https://pancreatitis.nl/studies/apec

Contact information

Type

Scientific

Primary contact

Prof M.J. Bruno

ORCID ID

Contact details

Erasmus Medical Center
Department of Gastroenterology and Hepatology
Doctor Molewaterplein 40
Rotterdam
3015 GD
Netherlands

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

www.erasmusmc.nl

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

Publication citations

Additional files

Editorial Notes