title: Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients.
  
  
  METHODS
  The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation.
  
  
  CONCLUSIONS
  The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, PO 2040, 3000, CA, Rotterdam, The Netherlands. n.schepers@pancreatitis.nl.|Department of Gastroenterology and Hepatology, St Antonius Hospital, PO 2500, 3430, EM, Nieuwegein, The Netherlands. n.schepers@pancreatitis.nl.
authors.forename: Nicolien J
authors.initials: NJ
authors.lastname: Schepers
authors.affiliation: Department of Surgery, University Medical Center Utrecht, PO 85500, 3508, GA, Utrecht, The Netherlands. o.j.bakker@umcutrecht.nl.
authors.forename: Olaf J
authors.initials: OJ
authors.lastname: Bakker
authors.affiliation: Department of Surgery, Academic Medical Center University of Amsterdam, PO 22660, 1100, DD, Amsterdam, The Netherlands. m.g.besseling@amc.nl.
authors.forename: Marc G H
authors.initials: MG
authors.lastname: Besselink
authors.affiliation: Department of Radiology, St Antonius Hospital, PO 2500, 3430, EM, Nieuwegein, The Netherlands. t.bollen@antoniusziekenhuis.nl.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Bollen
authors.affiliation: Clinical Research Unit, Academic Medical Center University of Amsterdam, PO 22660, 1100, DD, Amsterdam, The Netherlands. m.g.dijkgraaf@amc.nl.
authors.forename: Marcel G W
authors.initials: MG
authors.lastname: Dijkgraaf
authors.affiliation: Department of Surgery, Erasmus Medical Center, PO 2040, 3000, CA, Rotterdam, The Netherlands. c.vaneijck@erasmusmc.nl.
authors.forename: Casper H J
authors.initials: CH
authors.lastname: van Eijck
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center University of Amsterdam, PO 22660, 1100, DD, Amsterdam, The Netherlands. p.fockens@amc.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Fockens
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, HP 690, PO 9101, 6500, HB, Nijmegen, The Netherlands. erwin.vangeenen@radboudumc.nl.
authors.forename: Erwin J M
authors.initials: EJ
authors.lastname: van Geenen
authors.affiliation: Department of Surgery, Academic Medical Center University of Amsterdam, PO 22660, 1100, DD, Amsterdam, The Netherlands. j.vangrinsven@pancreatitis.nl.|Department of Gastroenterology and Hepatology, Academic Medical Center University of Amsterdam, PO 22660, 1100, DD, Amsterdam, The Netherlands. j.vangrinsven@pancreatitis.nl.
authors.forename: Janneke
authors.initials: J
authors.lastname: van Grinsven
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, PO 2040, 3000, CA, Rotterdam, The Netherlands. n.hallensleben@pancreatitis.nl.|Department of Surgery, St Antonius Hospital, PO 2500, 3430, EM, Nieuwegein, The Netherlands. n.hallensleben@pancreatitis.nl.
authors.forename: Nora D L
authors.initials: ND
authors.lastname: Hallensleben
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, PO 2040, 3000, CA, Rotterdam, The Netherlands. b.hansen@erasmusmc.nl.
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.affiliation: Department of Surgery, St Antonius Hospital, PO 2500, 3430, EM, Nieuwegein, The Netherlands. h.van.santvoort@antoniusziekenhuis.nl.
authors.forename: Hjalmar C
authors.initials: HC
authors.lastname: van Santvoort
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, PO 2040, 3000, CA, Rotterdam, The Netherlands. r.timmer@antoniusziekenhuis.nl.
authors.forename: Robin
authors.initials: R
authors.lastname: Timmer
authors.affiliation: Department of Gastroenterology and Hepatology, Sint Franciscus Gasthuis, PO 10900, 3004, BA, Rotterdam, The Netherlands. m.anten@sfvg.nl.
authors.forename: Marie-Paule G F
authors.initials: MP
authors.lastname: Anten
authors.affiliation: Department of Gastroenterology and Hepatology, Reinier de Graaf Hospital, Reinier de Graafweg 3-11, 2625, AD, Delft, The Netherlands. clemens@bolwerkdega.com.
authors.forename: Clemens J M
authors.initials: CJ
authors.lastname: Bolwerk
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center Amsterdam, PO Box 7057, 1007, MB, Amsterdam, The Netherlands. f.vandelft@vumc.nl.
authors.forename: Foke
authors.initials: F
authors.lastname: van Delft
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, PO 30001, 9700, RB, Groningen, The Netherlands. h.m.dullemen@umcg.nl.
authors.forename: Hendrik M
authors.initials: HM
authors.lastname: van Dullemen
authors.affiliation: Department of Gastroenterology and Hepatology, Gelre Hospital, PO 9014, 7300, DS, Apeldoorn, The Netherlands. w.erkelens@gelre.nl.
authors.forename: G Willemien
authors.initials: GW
authors.lastname: Erkelens
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center University of Amsterdam, PO 22660, 1100, DD, Amsterdam, The Netherlands. j.vanhooft@amc.nl.
authors.forename: Jeanin E
authors.initials: JE
authors.lastname: van Hooft
authors.affiliation: Department of Gastroenterology and Hepatology, St. Elisabeth Hospital, PO 90151, 5000, LC, Tilburg, The Netherlands. r.laheij@elisabeth.nl.
authors.forename: Robert
authors.initials: R
authors.lastname: Laheij
authors.affiliation: Department of Gastroenterology and Hepatology, Kennemer Gasthuis, PO 417, 2000, AK, Haarlem, The Netherlands. hulst@kg.nl.
authors.forename: René W M
authors.initials: RW
authors.lastname: van der Hulst
authors.affiliation: Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Postbus 95500, 1090, HM, Amsterdam, The Netherlands. j.m.jansen@olvg.nl.
authors.forename: Jeroen M
authors.initials: JM
authors.lastname: Jansen
authors.affiliation: Department of Gastroenterology and Hepatology, Maasstad Hospital, Maasstadweg 21, 3079, DZ, Rotterdam, The Netherlands. kubbenf@maasstadziekenhuis.nl.
authors.forename: Frank J G M
authors.initials: FJ
authors.lastname: Kubben
authors.affiliation: Department of Gastroenterology and Hepatology, Sint Lucas Andreas Hospital, PO 9243, 1006, AE, Amsterdam, The Netherlands. s.kuiken@slaz.nl.
authors.forename: Sjoerd D
authors.initials: SD
authors.lastname: Kuiken
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center Haaglanden, PO 432, 2501, CK Den Haag, The Netherlands. l.perk@mch.nl.
authors.forename: Lars E
authors.initials: LE
authors.lastname: Perk
authors.affiliation: Department of Gastroenterology and Hepatology, Maastricht University Medical Center, PO 5800, 6202, AZ, Maastricht, The Netherlands. r.de.ridder@mumc.nl.
authors.forename: Rogier J J
authors.initials: RJ
authors.lastname: de Ridder
authors.affiliation: Department of Gastroenterology and Hepatology, Amphia Hospital, PO 90158, 4800, RK, Breda, The Netherlands. mrijk@amphia.nl.
authors.forename: Marno C M
authors.initials: MC
authors.lastname: Rijk
authors.affiliation: Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, PO 90153, 5200, ME 's-Hertogenbosch, The Netherlands. t.romkens@jbz.nl.
authors.forename: Tessa E H
authors.initials: TE
authors.lastname: Römkens
authors.affiliation: Department of Gastroenterology and Hepatology, Catharina Hospital, PO 1350, 5602, ZA, Eindhoven, The Netherlands. erik.schoon@catharinaziekenhuis.nl.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Schoon
authors.affiliation: Department of Gastroenterology and Hepatology, Meander Medical Center, PO 1502, 3800, BM, Amersfoort, The Netherlands. mp.schwartz@meander.nl.
authors.forename: Matthijs P
authors.initials: MP
authors.lastname: Schwartz
authors.affiliation: Department of Gastroenterology and Hepatology, Rijnstate Hospital, PO 9555, 6800, TA, Arnhem, The Netherlands. m.spanier@rijnstate.nl.
authors.forename: B W Marcel
authors.initials: BW
authors.lastname: Spanier
authors.affiliation: Department of Gastroenterology and Hepatology, Canisius-Wilhelmina Hospital, PO 9015, 6500, GS, Nijmegen, The Netherlands. a.tan@cwz.nl.
authors.forename: Adriaan C I T L
authors.initials: AC
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology and Hepatology, Martini Hospital, PO 30033, 9700, RM, Groningen, The Netherlands. thijsw@mz.nl.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Thijs
authors.affiliation: Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, PO 50000, 7500, KA, Enschede, The Netherlands. n.venneman@mst.nl.
authors.forename: Niels G
authors.initials: NG
authors.lastname: Venneman
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, PO 85500, 3508, GA, Utrecht, The Netherlands. f.vleggaar@umcutrecht.nl.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Vleggaar
authors.affiliation: Department of Gastroenterology and Hepatology, Albert Schweitzer Hospital, PO 444, 3300, AK, Dordrecht, The Netherlands. w.vandevrie@asz.nl.
authors.forename: Wim
authors.initials: W
authors.lastname: van de Vrie
authors.affiliation: Department of Gastroenterology and Hepatology, Hospital Gelderse Vallei Ede, PO 9025, 6710, HN, Ede, The Netherlands. b.witteman@zgv.nl.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Witteman
authors.affiliation: Department of Operating Rooms - Evidence Based Surgery, Radboud University Nijmegen Medical Centre, HP 690, PO 9101, 6500, HB, Nijmegen, The Netherlands. hein.gooszen67@hotmail.com.
authors.forename: Hein G
authors.initials: HG
authors.lastname: Gooszen
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, PO 2040, 3000, CA, Rotterdam, The Netherlands. m.bruno@erasmusmc.nl.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Bruno
mesh_terms: D000208:Acute Disease; D001662:Biliary Tract Surgical Procedures / Q000379:methods*; D002758:Cholangiography; D002985:Clinical Protocols; D019299:Decompression, Surgical / Q000379:methods*; D006801:Humans; D010195:Pancreatitis / Q000601:surgery*; D018401:Sample Size; D016717:Sphincterotomy, Endoscopic