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Published in: Trials 1/2015

Open Access 01-12-2015 | Study protocol

Multimodal treatment of perianal fistulas in Crohn’s disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial

Authors: E. Joline de Groof, Christianne J. Buskens, Cyriel Y. Ponsioen, Marcel G. W. Dijkgraaf, Geert R. A. M. D’Haens, Nidhi Srivastava, Gijs J. D. van Acker, Jeroen M. Jansen, Michael F. Gerhards, Gerard Dijkstra, Johan F. M. Lange, Ben J. M. Witteman, Philip M. Kruyt, Apollo Pronk, Sebastiaan A. C. van Tuyl, Alexander Bodelier, Rogier M. P. H. Crolla, Rachel L. West, Wietske W. Vrijland, Esther C. J. Consten, Menno A. Brink, Jurriaan B. Tuynman, Nanne K. H. de Boer, Stephanie O. Breukink, Marieke J. Pierik, Bas Oldenburg, Andrea E. van der Meulen, Bert A. Bonsing, Antonino Spinelli, Silvio Danese, Matteo Sacchi, Janindra Warusavitarne, Ailsa Hart, Nuha A. Yassin, Rory P. Kennelly, Garret J. Cullen, Desmond C. Winter, A. Barney Hawthorne, Jared Torkington, Willem A. Bemelman

Published in: Trials | Issue 1/2015

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Abstract

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/Design

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.

Discussion

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.

Trial registration

Nederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).
Appendix
Available only for authorised users
Literature
1.
Hellers G, Bergstrand O, Ewerth S, Holmstrom B. Occurrence and outcome after primary treatment of anal fistulae in Crohn’s disease. Gut. 1980;21:525–7.CrossRefPubMedPubMedCentral
2.
Vigano C, Losco A, Caprioli F, Basilisco G. Incidence and clinical outcomes of intersphincteric abscesses diagnosed by anal ultrasonography in patients with Crohn’s disease. Inflamm Bowel Dis. 2011;17:2102–8.CrossRefPubMed
3.
Buchanan GN, Owen HA, Torkington J, Lunniss PJ, Nicholls RJ, Cohen CR. Long-term outcome following loose-seton technique for external sphincter preservation in complex anal fistula. Br J Surg. 2004;91:476–80.CrossRefPubMed
4.
Tanaka S, Matsuo K, Sasaki T, Nakano M, Sakai K, Beppu R, et al. Clinical advantages of combined seton placement and infliximab maintenance therapy for perianal fistulizing Crohn’s disease: when and how were the seton drains removed? Hepatogastroenterology. 2010;57:3–7.PubMed
5.
Soltani A, Kaiser AM. Endorectal advancement flap for cryptoglandular or Crohn’s fistula-in-ano. Dis Colon Rectum. 2010;53:486–95.CrossRefPubMed
6.
Osterman MT, Lichtenstein GR. Infliximab in fistulizing Crohn’s disease. Gastroenterol Clin North Am. 2006;35:795–820.CrossRefPubMed
7.
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340:1398–405.CrossRefPubMed
8.
Lichtiger S, Binion DG, Wolf DC, Present DH, Bensimon AG, Wu E, et al. The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn’s disease who failed prior infliximab therapy. Aliment Pharmacol Ther. 2010;32:1228–39.CrossRefPubMed
9.
Arnott ID, McDonald D, Williams A, Ghosh S. Clinical use of infliximab in Crohn’s disease: the Edinburgh experience. Aliment Pharmacol Ther. 2001;15:1639–46.CrossRefPubMed
10.
Ardizzone S, Colombo E, Maconi G, Bollani S, Manzionna G, Petrone MC, et al. Infliximab in treatment of Crohn’s disease: the Milan experience. Dig Liver Dis. 2002;34:411–8.CrossRefPubMed
11.
Poritz LS, Rowe WA, Koltun WA. Remicade does not abolish the need for surgery in fistulizing Crohn’s disease. Dis Colon Rectum. 2002;45:771–5.CrossRefPubMed
12.
Orlando A, Colombo E, Kohn A, Biancone L, Rizzello F, Viscido A, et al. Infliximab in the treatment of Crohn’s disease: predictors of response in an Italian multicentric open study. Dig Liver Dis. 2005;37:577–83.CrossRefPubMed
13.
Miheller P, Lakatos PL, Horvath G, Molnar T, Szamosi T, Czegledi Z, et al. Efficacy and safety of infliximab induction therapy in Crohn’s Disease in Central Europe--a Hungarian nationwide observational study. BMC Gastroenterol. 2009;9:66.CrossRefPubMedPubMedCentral
14.
Lichtenstein GR, Yan S, Bala M, Blank M, Sands BE. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn’s disease. Gastroenterology. 2005;128:862–9.CrossRefPubMed
15.
Sands BE, Blank MA, Diamond RH, Barrett JP, van Deventer SJ. Maintenance infliximab does not result in increased abscess development in fistulizing Crohn’s disease: results from the ACCENT II study. Aliment Pharmacol Ther. 2006;23:1127–36.CrossRefPubMed
16.
Van AG, Vanbeckevoort D, Bielen D, Coremans G, Aerden I, Noman M, et al. Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn’s disease. Am J Gastroenterol. 2003;98:332–9.CrossRef
17.
Lamers LM, Stalmeier PF, McDonnell J, Krabbe PF, van Busschbach JJ. Measuring the quality of life in economic evaluations: the Dutch EQ-5D tariff. Ned Tijdschr Geneeskd. 2005;149:1574–8.PubMed
18.
19.
Mauskopf JA, Sullivan SD, Annemans L, Caro J, Mullins CD, Nuijten M, et al. Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices--budget impact analysis. Value Health. 2007;10:336–47.CrossRefPubMed
20.
Dewint P, Hansen BE, Verhey E, Oldenburg B, Hommes DW, Pierik M, et al. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn’s disease: a randomised, double-blind, placebo controlled trial (ADAFI). Gut. 2013;63:292–9.CrossRefPubMed
21.
Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–95.CrossRefPubMed
22.
Van AG, Dignass A, Reinisch W, van der Woude CJ, Sturm A, De VM, et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: special situations. J Crohns Colitis. 2010;4:63–101.CrossRef
23.
Morrison JG, Gathright Jr JB, Ray JE, Ferrari BT, Hicks TC, Timmcke AE. Surgical management of anorectal fistulas in Crohn’s disease. Dis Colon Rectum. 1989;32:492–6.CrossRefPubMed
24.
Williams JG, Rothenberger DA, Nemer FD, Goldberg SM. Fistula-in-ano in Crohn’s disease. Results of aggressive surgical treatment. Dis Colon Rectum. 1991;34:378–84.CrossRefPubMed
25.
Scott HJ, Northover JM. Evaluation of surgery for perianal Crohn’s fistulas. Dis Colon Rectum. 1996;39:1039–43.CrossRefPubMed
26.
Takesue Y, Ohge H, Yokoyama T, Murakami Y, Imamura Y, Sueda T. Long-term results of seton drainage on complex anal fistulae in patients with Crohn’s disease. J Gastroenterol. 2002;37:912–5.CrossRefPubMed
27.
Chung W, Ko D, Sun C, Raval MJ, Brown CJ, Phang PT. Outcomes of anal fistula surgery in patients with inflammatory bowel disease. Am J Surg. 2010;199:609–13.CrossRefPubMed
Metadata
Title
Multimodal treatment of perianal fistulas in Crohn’s disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial
Authors
E. Joline de Groof
Christianne J. Buskens
Cyriel Y. Ponsioen
Marcel G. W. Dijkgraaf
Geert R. A. M. D’Haens
Nidhi Srivastava
Gijs J. D. van Acker
Jeroen M. Jansen
Michael F. Gerhards
Gerard Dijkstra
Johan F. M. Lange
Ben J. M. Witteman
Philip M. Kruyt
Apollo Pronk
Sebastiaan A. C. van Tuyl
Alexander Bodelier
Rogier M. P. H. Crolla
Rachel L. West
Wietske W. Vrijland
Esther C. J. Consten
Menno A. Brink
Jurriaan B. Tuynman
Nanne K. H. de Boer
Stephanie O. Breukink
Marieke J. Pierik
Bas Oldenburg
Andrea E. van der Meulen
Bert A. Bonsing
Antonino Spinelli
Silvio Danese
Matteo Sacchi
Janindra Warusavitarne
Ailsa Hart
Nuha A. Yassin
Rory P. Kennelly
Garret J. Cullen
Desmond C. Winter
A. Barney Hawthorne
Jared Torkington
Willem A. Bemelman
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Trials / Issue 1/2015
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-015-0831-x

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