The objective of the study is to investigate whether early ERC plus ES in patients with suspected APB and a predicted severe disease course without cholangitis, lowers the incidence of a composite endpoint of mortality and severe morbidity. Major…
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
- Bile duct disorders
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incidence of a composite endpoint of mortality and severe complications.
Major Complications are considered as (for definitions see protocol Appendix
Table 3):
- organ failure
- pancreatic necrosis
- bacteremia
- cholangitis
- pneumonia
- exocrine and/ or endocrine pancreatic insufficiency
Secondary outcome
Incidence of all individual components of the primary endpoint, length of
hospital stay, new onset intensive care admission, length of intensive care
stay, respiratory complications, cholangitis during admission, ERC-related
complications, number of endoscopic, radiological and operative (re-)
interventions, readmission for biliary events, difficulty of cholecystectomy
and cost-effectiveness with direct medical and non-medical and indirect costs.
Background summary
Acute biliary pancreatitis (ABP) is a serious illness with an overall mortality
rate ranging from 1% for mild pancreatitis to around 20% for infected
necrotizing pancreatitis. In the majority of cases the causative and initiating
events are passage and impaction of biliary stones and sludge in the common
bile duct and ampulla. Early relief of obstruction and removal of stones and
sludge by endoscopic retrograde cholangiography (ERC) and endoscopic
sphincterotomy (ES) may prevent the disease to deteriorate to (infected)
necrotizing pancreatitis, thereby reducing mortality and morbidity rates
substantially.
Study objective
The objective of the study is to investigate whether early ERC plus ES in
patients with suspected APB and a predicted severe disease course without
cholangitis, lowers the incidence of a composite endpoint of mortality and
severe morbidity. Major morbidity is further discussed under the heading
"primary and secondary endpoints".
Furthermore this study investigates if the addition of a diagnostic EUS,
followed by ERC with ES in case of gallstones/sludge can further reduce the
composite endpoint.
Study design
Randomized, superiority, assessor-blinded multicenter trial with a follow-up of
6 months after randomisation for primary and secondary endpoints, followed by a
prospective multicenter cohort with a similar protocol and follow-up.
Intervention
Intervention: Early (<24 hrs after admission and < 72 hrs after start symptoms)
ERC plus ES.
Comparison: Conservative (expectative) management with delayed intervention
only when clinically indicated.
Prospective cohort: Early (<24 hrs after admission and < 72 hrs after start
symptoms) EUS-guided ERC with ES
Study burden and risks
Patients included in the early ERC plus ES group are exposed to the normal
complications associated with an ERC with ES. ERC's will carried out by, or
under direct supervision of, an experienced interventional endoscopist.
Complications which might occur are performation, bleeding, respiratory
insufficiëncy, cardiovascular complications or the development of a post-ERC
pancreatitis. Patients allocated to conservative treatment will not undergo
early ERC unless he/ she develops a cholangitis. To date no adequately designed
trial has been performed to definitely define the role of ERC plus ES in
patients with a predicted severe acute biliary pancreatitis. Estimated
beneficial risks of ERC in proportion to the normal ERC-related complications
are difficult to assess. However, the hypothesis is that an early ERC plus ES
ameloriates the disearse course. To prove this a randomised controlled clinical
trial is urgently needed.
Experimental studies indicate that only in case of mechanical obstruction of
the ampulla, an ERC with sphincterotomy can be usefull. Patients in whom
gallstones/sludge have passed into the duodenum spontaneously probably have no
benefit form this intervention. EUS can reliably evaluate the presence of
gallstones/sludge in de common bile duct and has recently become available in
most Dutch hospitals. Investigating if early EUS-guided ERC with ES in this
patient population can further ameliorate the treatment compared to
conservative treatment or ERC with ES is indicated. EUS can on the one hand
potentially reduce the amount of ERC procedures and their accompanying
procedural risks and can on the other hand warrant direct treatment for
patients with visible common bile duct obstruction.
's Gravendijkwal 230
Rotterdam 3015CE
NL
's Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
1. Acute pancreatitis, defined as the presence of at least 2 out of the following 3 criteria:
- upper abdominal pain
- serum amylase and/ or lipase concentration >3 times the upper limit of normal
- signs of pancreatitis on CT or MR
2. Predicted severe course of the acute pancreatitis based on either one of the following positieve scores:
- CRP >150mg/L
- Imrie score * 3
- APACHE II score * 8
3. High probability acute biliary pancreatitis: see criterion 1 and at least one of the following criteria:
- gallstones and/ or biliary sludge on imaging (US, CT of MR)
- a dilated common bile duct on imaging (US, CT of MR) defined as >8mm in patients * 75 years or >10mm in patients >75 years
- ALAT > two times upper limit of normal
4. ERC can be performed within 24 hours after admission, but no more than 72 hours after the start of symtoms
5. Age >18 year old
6. Written informed consent
7. In case of a previous episode of necrotizing pancreatitis, patient should be fully recovered (confirmed on imaging)
Exclusion criteria
1. Cholangitis
2. Acute pancreatitis due to other causes such as alcohol abuse (either chronic or binge drinking), metabolic causes, medication, trauma, etc.
3. Pregnancy
4. Previous precut sphincterotomy and/ or ES
5. INR that cannot be corrected with co-fact or FFP below 1.5
6. Chronic pancreatitis
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 |
|---|---|
| ISRCTN | ISRCTN97372133 |
| CCMO | NL39745.078.12 |