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

Abstract

BackgroundCurrently 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/DesignThis 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.DiscussionThe 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 registrationNederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0831-x) contains supplementary material, which is available to authorized users.

Modern management of perianal fistulas in Crohn’s disease: future directions

“…The multimodal treatment of perianal fistulas in Crohn’s disease: seton versus anti-TNF versus advancement plasty ( PISA ) trial is actively recruiting with the aim to compare what the optimal surgical and medical strategy may be 34. After seton placement and sepsis drainage, patients will be randomised into three groups: chronic setons+6-MP; anti-TNF+6 MP (seton withdrawal after 6 weeks) and mucosal advancement plasty.…”

Systematic review of surgical interventions for Crohn's anal fistula

“…Since searches for this review were performed, a randomized trial of stem cells has been reported80. A randomized trial of advancement flap versus seton drainage in the context of protocolled medical therapy is underway81.…”

Review article: pathogenesis of Crohn's perianal fistula—understanding factors impacting on success and failure of treatment strategies

“…Some studies have utilised this function of a seton but are aware of the concern that epithelialisation may occur if it is left too long and this may hinder response to medical or surgical treatment. In the ongoing PISA ( Treatment of Perianal FIstulas in Crohn's Disease: Seton vs Anti‐TNF vs Advancement Plasty ) study, still recruiting and not due to report for some time, all 3 arms (chronic loose seton, anti‐TNF agent induction and maintenance, anti‐TNF agent induction and advancement flap repair) start with loose seton insertion and a 2‐week course of antibiotics to reduce inflammation . In the anti‐TNF group, the seton will be removed at 6 weeks (after infliximab induction).…”