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

NCT06441526 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: NL66176.018.18
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

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.

Conditions

Perianal Fistula; Crohn Disease

Keywords

Crohn's disease; Perianal fistula; Anti-TNF; Advancement plasty; LIFT-procedure; Fistula closure; Comprehensive cohort design

Outcome Measures

Primary Outcomes (1)

• Fistula closure

  The number of patients with radiologically closed (completely fibrotic) fistula tract on MRI

  at 1,5 year

Secondary Outcomes (5)

• Clinical closure

  at 1,5 year

• The number of patients undergoing surgical re-intervention

  at 1,5 year

• The number of re-intervention

  at 1,5 year

• The quality of life of a patient

  Every six months from baseline till 18 months

• The number of recurrences

  at 1,5 year

Study Arms (2)

Anti-TNF

ACTIVE COMPARATOR

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.

Drug: anti-tumour necrosis factor α antibodies

Surgical closure

ACTIVE COMPARATOR

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.

Procedure: Advancement plasty

Interventions

anti-tumour necrosis factor α antibodies DRUG

Biological drug

Anti-TNF

Advancement plasty PROCEDURE

Surgical closure of the internal opening

Also known as: Ligation of the intersphincteric tract (LIFT)

Surgical closure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years
• (re-)active perianal fistula
• High perianal fistula tract (intersphincteric, transsphincteric, suprasphincteric) located in the upper two-thirds of the external sphincter or puborectal muscle
• Fistula with one internal opening (based on MRI imaging). The number of external fistulas does not have to be taken into account
• Written informed consent

You may not qualify if:

• Proctitis (defined as any active mucosal inflammation or ulcer \> 5mm in the rectum)
• Anorectal stenosis (defined as the impossibility to introduce a proctoscope)
• Submucosal fistulas \& low intersphincteric fistulas (lower one-third of external sphincter)
• Rectovaginal fistula
• Multiple internal openings
• Use of Anti-TNF medication for more than 3 months
• Previous failure of Anti-TNF treatment for perianal fistula
• Patients with a stoma
• Dementia or altered mental status that would prohibit the understanding and giving of informed consent

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC

Amsterdam-Zuidoost, North Holland, 1105AZ, Netherlands

Location

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Willem Bemelman, MD PhD

  Amsterdam UMC, location AMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The primary outcome is fistula closure based on MRI (completely fibrotic fistula tract). A radiologist blinded to treatment allocation will score fibrosis and inflammation of the tract based on MRI.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: This is an international, multicentre, prospective, comprehensive cohort design trial to identify the most optimal treatment of Crohn's high perianal fistulas. In a comprehensive cohort design patients with a preference will be treated accordingly, whereas only those indifferent to treatment will be randomised in the usual way (combined randomised and preference cohort).

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: June 4, 2024
• Study Start: September 14, 2013
• Primary Completion: December 7, 2019
• Study Completion: June 7, 2021
• Last Updated: June 4, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

NL (1)