Surgical Closure vs Anti-TNF in the Treatment of Perianal Fistulas in Crohn's Disease (PISA-II): a Comprehensive Cohort Design

Phase 3

Completed

• Conditions: Crohn Disease; Perianal Fistula
• Interventions: Drug: anti-tumour necrosis factor α antibodies; Procedure: Advancement plasty

• Registration Number: NCT06441526
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

Currently, the treatment of Crohn's patients with perianal fistulas predominantly exists of anti-TNF medication. However, its efficiency has never been directly compared to surgical closure of the perianal fistula. The aim of this study is to compare radiological fistula healing at MRI after 18 months follow-up in Crohn's patients undergoing surgical closure to anti-TNF medication as treatment of perianal Crohn's fistulas.

Study design: In this multicenter comprehensive cohort design (CCD) Crohn's patients with a (re)active high perianal fistula will be allocated to anti-TNF for 1 year or surgical closure after 2 months under a short course of anti-TNF. Patients with a distinct preference will be treated accordingly, whereas only indifferent patients will be randomised in the usual way.

Main study parameters/endpoints: The primary outcome parameter is the number of patients with radiologically closed fistulas based on an evaluated MRI-score after 18 months. Secondary outcomes are clinical closure, number of patients undergoing surgical re-interventions and number of re-interventions, recurrences and quality of life based on the Perianal Disease Activity Index (PDAI).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All patients will receive one of the two standard treatment approaches that are currently used for Crohn's fistulas. All effort has been performed to ensure most optimal treatment, according to best available evidence and current guidelines. Since there is no experimental study-arm, there are no additional risks associated with participation. During the study, the medical staff and trial nurses will monitor the necessity of surgical interventions and hospitalizations. At baseline and after 18 months all patients will undergo a MRI to score the fistula. Secondary outcome parameters will be assessed during visits to the outpatient clinic or telephone consultations at baseline and at intervals of 3 months for the duration of the study period. Every 6 months patients were asked to fill out the PDAI questionnaire with their physician. Based on the available literature, radiological closure of fistulas is expected in 40% of patients in the surgical closure group compared to 15% in the anti-TNF group. The increase in closure rate from 15% to 40% is considered clinically relevant. Due to the combination of a preference and randomized cohort, the appropriate sample size to detect this 25% difference is flexible and is adjusted for a skewed distribution. The minimal sample size, in case of a 1:1 treatment allocation, needed to detect this difference with a Chi-square test equals 86 patients (alpha 0.05, power 80%). The maximal allowed skewed distribution is set at 1:4, which will result in a maximal sample size of 116 patients.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-14
• Study First Submitted: 2019-04-10
• Primary Completion: 2019-12-07
• Study Completion: 2021-06-07
• Status Verified: 2024-06
• Study First Submitted QC: 2024-06-01
• Last Update Submitted: 2024-06-01
• Study First Posted: 2024-06-04
• Last Update Posted: 2024-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 94

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anti-TNF	anti-tumour necrosis factor α antibodies	Seton placement, followed by anti-TNF medication (infliximab or adalimumab) in combination with a immunomodulator after ± 2 weeks. The seton will be removed after ± 6 weeks. Continuation of anti-TNF medication for at least 1 year, after one year continuation is at the discretion of treating physician.
Surgical closure	Advancement plasty	Seton placement, followed by anti-TNF medication in combination with a immunomodulator after ± 2 weeks. After 8-10 weeks removal of seton and surgical closure (advancement plasty or ligation of the intersphincteric tract (LIFT) procedure). Anti-TNF in combination with a immunomodulator will be stopped after ± 4 months.

Primary Outcome Measures

Name	Time	Method
Fistula closure	at 1,5 year	The number of patients with radiologically closed (completely fibrotic) fistula tract on MRI

Secondary Outcome Measures

Name	Time	Method
The number of re-intervention	at 1,5 year	Amount of re-interventions
Clinical closure	at 1,5 year	The number of patients with clinical closure, defined as closure of the external opening without discharge of pus or faeces on palpation
The number of patients undergoing surgical re-intervention	at 1,5 year	Amount of patients undergoing surgical re-intervention
The quality of life of a patient	Every six months from baseline till 18 months	measured by the Perianal Disease Activity Index (PDAI score)
The number of recurrences	at 1,5 year	Amount of patients with a recurrence, defined as re-opening of the external opening after clinical closure

Trial Locations

Locations (1)

Amsterdam UMC; 🇳🇱 Amsterdam-Zuidoost, Noord Holland, Netherlands