INTRODUCTION While most patients with acute pancreatitis suffer a mild and uncomplicated
course of disease, up to 20% develop a more severe course with development of pancreatic
and/or peripancreatic necroses. With time, these necroses become encapsulated with a
well-defined inflammatory wall, so called walled-off necroses (WONs). Up to 30% of WONs
become infected, which prolongs the length of hospital stay (LOS), increases morbidity
and mortality significantly, and generally requires some kind of invasive intervention.
During the last two decades, a minimally invasive step-up approach consisting of
percutaneous and/or endoscopic, transluminal drainage followed, if necessary, by
percutaneous, video-assisted retroperitoneal debridement (VARD) or endoscopic
necrosectomy (EN), have replaced open surgery as the standard treatment resulting in
improved patient outcomes. Copenhagen University Hospital Hvidovre have for nearly two
decades treated more than 400 WON patients with an actual annual number of 40-50
patients. This center serves as a tertiary referral center, the only in East-Denmark,
with a background population of 2.6 million. In line with international guidelines,
endoscopic step-up approach has been practiced as standard care for infected WONs. This
approach follows international recommendations of delaying index procedures until at
least four weeks after debut of pancreatitis (to ensure encapsulation) and then only
applying the least invasive intervention needed. The decision to step-up is triggered by
absence of biochemical and/or clinical improvement or clinical deterioration.
Recently, lumen-apposing metal stents (LAMS) have been introduced for the transluminal
treatment of pancreatic fluid collections. The stent is fully-covered and shaped with two
bilateral anchor flanges with a saddle in between. A dedicated through-the-scope delivery
system, where the tip serves as an electrocautery device enables extra-luminal access and
deployment of the stent. Conventionally, transmural drainage with installation of two
double pigtail plastic stents (DPS) has been the method of choice. Although drainage with
plastic stents seems non-inferior to LAMS, the DPS method implies a need for repetitive
dilatation of the drainage tract because of spontaneous closure of the tract and thereby
probably a higher number of endoscopic procedures. By keeping the transmural tract
patent, LAMS may improve drainage and facilitate endoscopic necrosectomy, which may even
be performed during the index procedure (direct endoscopic necrosectomy (DEN)).
The LOS is considerable for patients treated for infected WON, especially those with
complex and large fluid collections. Copenhagen University Hvidovre Hospital has one of
the largest prospective single center databases registering all patients treated with
WON. The median LOS for patients with large WONs exceeding 15 cm in diameter treated with
the step-up approach, is 58 days. During the hospital stay, patients undergo weekly
endoscopic or surgical procedures, and many patients additionally need treatment in the
intensive care unit. Together, the treatment of patients with WON carries a substantial
economic burden for the health care system. Furthermore, even in a tertiary care setting,
the mortality is still up to 15% in complex cases with large fluid collections. The
mortality in patient needing treatment in intensive care unit (ICU) is much higher,
nearly 40%. Unprotocolized cases with urgent needs for an augmented course of treatment
(e.g. cases with malignancy demanding surgery or oncological therapy) have been
successfully treated with an accelerated treatment algorithm. Likewise, an international
multicenter study found that an aggressive treatment was safe with promising results. The
invastegators hypothesize, that a general alteration in the treatment algorithm
instigating an aggressive treatment algorithm instead of a classical step-up approach
might not only shorten LOS, but also reduce the mortality in patients treated for large
WONs.
AIM To compare a conventional endoscopic step-up approach with an accelerated treatment
algorithm using DEN.
STUDY DESIGN A single-center open-label, randomized, controlled 2 armed superiority
study.
Patients with acute, necrotizing pancreatitis and WON exceeding a diameter of 15 cm will
be randomized to either the endoscopic step-up approach or direct endoscopic
necrosectomy.
The primary endpoint is a composite of death, major complications occurring within 6
months following randomization, or length of stay exceeding 58 days.
From results previously published by Copenhagen University Hospital Hvidovre, it is shown
that the risk of death for eligible patients is estimated to 5%, the risk of major
complications is 5%, while the risk of exceeding a LOS of above 58 days is 50%. The
investigators assume that the risk of death and major complications will remain at 5% and
5%, respectively, while the rate of patients exceeding a LOS of 58 days will be reduced
by 75% to 12.5%. Based on these estimates, 48 patients are required to have an 80% change
(5% significant level) of detecting an increase in success rate in the primary outcome
measure from 40% in the control group to 77.5% in the interventional group.
The investigators will after inclusion of 25 patients conduct an interim analysis to
assess whether one of the study groups are superior to an extent that will ethically call
for an early termination of the study. Likewise, safety will continually be assessed in
conjunction with the ethics committee.