Multimodal treatment of perianal fistulas in Crohn's disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial.
BACKGROUND
Currently there is no guideline for the treatment of patients with Crohn's disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs.


METHODS
This is a multicentre, randomized controlled trial. Patients with Crohn's disease who are over 18 years of age, with newly diagnosed or recurrent active high perianal fistulas, with one internal opening and no anti-TNF usage in the past three months will be considered. Patients with proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to randomisation, an MRI and ileocolonoscopy are required. All treatment will start with seton placement and a course of antibiotics. Patients will then be randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after six weeks) or (3) advancement plasty after eight weeks of seton drainage (under four months anti-TNF and 6MP for one year). The primary outcome parameter is the number of patients needing fistula-related re-intervention(s). Secondary outcomes are the number of patients with closed fistulas (based on an evaluated MRI score) after 18 months, disease activity, quality of life and costs.


CONCLUSIONS
The PISA trial is a multicentre, randomised controlled trial of patients with Crohn's disease and high perianal fistulas. With the comparison of three generally accepted treatment strategies, we will be able to comment on the efficiency of the various treatment strategies, with respect to several long-term outcome parameters.


BACKGROUND
Nederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).
Department of Surgery, Academic Medical Center, PO Box 22660, 1100, DD, Amsterdam, The Netherlands. e.j.degroof@amc.uva.nl.|Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. e.j.degroof@amc.uva.nl.
E Joline
EJ
de Groof
Department of Surgery, Academic Medical Center, PO Box 22660, 1100, DD, Amsterdam, The Netherlands. c.j.buskens@amc.uva.nl.
Christianne J
CJ
Buskens
Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.y.ponsioen@amc.uva.nl.
Cyriel Y
CY
Ponsioen
Clinical Research Unit, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.g.dijkgraaf@amc.uva.nl.
Marcel G W
MG
Dijkgraaf
Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. g.dhaens@amc.uva.nl.
Geert R A M
GR
D'Haens
Department of Gastroenterology and Hepatology, Medical Center Haaglanden, Lijnbaan 32, 2512 VA Den Haag, The Netherlands. n.srivastava@mchaaglanden.nl.
Nidhi
N
Srivastava
Department of Surgery, Medical Center Haaglanden, Lijnbaan 32, 2512 VA Den Haag, The Netherlands. g.van.acker@mchaaglanden.nl.
Gijs J D
GJ
van Acker
Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Oosterpark 9, 1091 AC Amsterdam, The Netherlands. j.m.jansen@olvg.nl.
Jeroen M
JM
Jansen
Department of Surgery, Onze Lieve Vrouwe Gasthuis, Oosterpark 9, 1091 AC Amsterdam, The Netherlands. m.f.gerhards@olvg.nl.
Michael F
MF
Gerhards
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. g.dijkstra@int.umcg.nl.
Gerard
G
Dijkstra
Department of Surgery, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. j.lange@umcg.nl.
Johan F M
JF
Lange
Department of Gastroenterology and Hepatology, Hospital Gelderse Vallei, Willy Brandtlaan 10, 6716 RP Ede, The Netherlands. WittemanB@zgv.nl.
Ben J M
BJ
Witteman
Department of Surgery, Hospital Gelderse Vallei, Willy Brandtlaan 10, 6716 RP Ede, The Netherlands. KruytF@zgv.nl.
Philip M
PM
Kruyt
Department of Surgery, Diakonessenhuis Utrecht, Bosboomstraat 1, 3582 KE Utrecht, The Netherlands. APronk@diakhuis.nl.
Apollo
A
Pronk
Department of Gastroenterology and Hepatology, Diakonessenhuis Utrecht, Bosboomstraat 1, 3582 KE Utrecht, The Netherlands. bvtuyl@diakhuis.nl.
Sebastiaan A C
SA
van Tuyl
Department of Gastroenterology and Hepatology, Amphia Hospital, Molengracht 21, 4818 CK Breda, The Netherlands. abodelier@amphia.nl.
Alexander
A
Bodelier
Department of Surgery, Amphia Hospital, Molengracht 21, 4818 CK Breda, The Netherlands.
Rogier M P H
RM
Crolla
Department of Gastroenterology and Hepatology, St Franciscus Gasthuis, Kleiweg 500, 3045 PM Rotterdam, The Netherlands. r.west@sfg.n.
Rachel L
RL
West
Department of Surgery, St Franciscus Gasthuis, Kleiweg 500, 3045 PM Rotterdam, The Netherlands. w.vrijland@sfg.nl.
Wietske W
WW
Vrijland
Department of Surgery, Meander Medical Center, Maatweg 3, 3813 TZ Amersfoort, The Netherlands. ecj.consten@meandermc.nl.
Esther C J
EC
Consten
Department of Gastroenterology and Hepatology, Meander Medical Center, Maatweg 3, 3813 TZ Amersfoort, The Netherlands. ma.brink@meandermc.nl.
Menno A
MA
Brink
Department of Surgery, VU Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. j.tuynman@vumc.nl.
Jurriaan B
JB
Tuynman
Department of Gastroenterology and Hepatology, VU Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. KHN.deBoer@vumc.nl.
Nanne K H
NK
de Boer
Department of Surgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. s.breukink@mumc.nl.
Stephanie O
SO
Breukink
Department of Gastroenterology and Hepatology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. m.pierik@mumc.nl.
Marieke J
MJ
Pierik
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. b.oldenburg@umcutrecht.nl.
Bas
B
Oldenburg
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. ae.meulen@lumc.nl.
Andrea E
AE
van der Meulen
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. B.A.Bonsing@lumc.nl.
Bert A
BA
Bonsing
Department of Surgery, Humanitas Hospital, Via Alessandro Manzoni, 56, 20089 Rozzano MI, Milan, Italy. antonino.spinelli@humanitas.it.
Antonino
A
Spinelli
Department of Gastroenterology and Hepatology, Humanitas Hospital, Via Alessandro Manzoni, 56, 20089 Rozzano MI, Milan, Italy. silvio.danese@humanitas.it.
Silvio
S
Danese
Department of Surgery, Humanitas Hospital, Via Alessandro Manzoni, 56, 20089 Rozzano MI, Milan, Italy. matteo.sacchi@humanitas.it.
Matteo
M
Sacchi
Department of Surgery, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, London, UK. j.warusavitarne@nhs.net.
Janindra
J
Warusavitarne
Department of Gastroenterology and Hepatology, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, London, England. ailsa.hart@nhs.net.
Ailsa
A
Hart
Department of Surgery, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, London, UK. nuhayassin@nhs.net.
Nuha A
NA
Yassin
Department of Surgery, St Vincent's Healthcare Group, Elm Park, Merrion Rd, Dublin 4, Ireland. rorykennelly@rcsi.ie.
Rory P
RP
Kennelly
Department of Gastroenterology and Hepatology, St Vincent's Healthcare Group, Elm Park, Merrion Rd, Dublin 4, Ireland. g.cullen@st-vincents.ie.
Garret J
GJ
Cullen
Department of Surgery, St Vincent's Healthcare Group, Elm Park, Merrion Rd, Dublin 4, Ireland. des.winter@gmail.com.
Desmond C
DC
Winter
Department of Gastroenterology and Hepatology, Spire Cardiff Hospital, Glamorgan House, Croescadarn Rd, Cardiff, South Glamorgan CF23 8XL, UK. Barney.Hawthorne@wales.nhs.uk.
A Barney
AB
Hawthorne
Department of Surgery, Spire Cardiff Hospital, Glamorgan House, Croescadarn Rd, Cardiff, South Glamorgan CF23 8XL, England. Jared.Torkington@wales.nhs.uk.
Jared
J
Torkington
Department of Surgery, Academic Medical Center, PO Box 22660, 1100, DD, Amsterdam, The Netherlands. w.a.bemelman@amc.uva.nl.
Willem A
WA
Bemelman
D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003362:Cost-Benefit Analysis; D003424:Crohn Disease / Q000175:diagnosis / Q000191:economics / Q000276:immunology / Q000628:therapy*; D013505:Digestive System Surgical Procedures / Q000009:adverse effects / Q000191:economics / Q000379:methods*; D004322:Drainage / Q000009:adverse effects / Q000191:economics / Q000379:methods*; D004359:Drug Therapy, Combination; D005060:Europe; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D017048:Health Care Costs; D006801:Humans; D008279:Magnetic Resonance Imaging; D015122:Mercaptopurine / Q000627:therapeutic use; D011788:Quality of Life; D012003:Rectal Fistula / Q000175:diagnosis / Q000191:economics / Q000276:immunology / Q000628:therapy*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D015122:Mercaptopurine