Fistulodesis Pilot Study for Closure of Perianal Fistulae

Local Installation of Acetylcysteine, Doxycycline and Fibrin Glue and Surgical Closure of Fistula Openings for Treatment of Perianal Fistulae. An Open Label, Prospective, Multicentric Pilot Study

In this pilot study a new surgical treatment approach for perianal fistulae, called Fistulodesis, is performed. The study aims to assess effectiveness, safety and tolerability of the Fistulodesis procedure. The investigators are aiming to include 20 patients with Crohn's disease and 20 patients without underlying Crohn's disease. It is an open label study with an anticipated duration from January 2017 to January 2020.

Study Overview

• Status: Unknown
• Conditions: Crohn Disease; Perianal Fistula
• Intervention / Treatment: Procedure: Fistulodesis

Detailed Description

The investigators want to test Fistulodesis as a new treatment option which combines established low-invasive surgical and medical treatment steps with the local application of acetylcysteine, doxycycline and fibrin glue in the fistula tract.

Fistulodesis comprises the following steps:

• Curettage of fistula tract
• Mini-excision of the inner (endoanal) fistula opening
• Flushing of fistula tract with acetylcysteine
• Flushing/ filling of the fistula tract with doxycycline
• Filling the fistula tract with fibrin glue
• Surgical closure of inner (rectal) and outer (skin) fistula openings with a Z-suture
• Antibiotic treatment with metronidazole/ ciprofloxacin for 10 days after surgery

Agglutination of the fistula tract is a central part of this study. Agglutinative properties of doxycycline are frequently used by pneumologists for pleurodesis (artificial adhesion of the pleurae to occlude the pleural space for the treatment of pneumothorax or other conditions). Doxycycline (or tetracycline) is thereby instilled into the pleural space, leading to local inflammation and finally pleurodesis. Pleurodesis is an efficient procedure with closure rates >80%. The investigators are expecting to achieve high closure rates also for fistulae.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Recruiting
    • Division of Gastroenterology, University Hospital Zurich
  • Zürich, Switzerland
    • Recruiting
    • Bethanien-Klinik
    • Contact: Daniela Zeller, MD; Phone Number: +41 43 244 93 90; Email: daniela.zeller@bethanien.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients:

  • Signed informed consent
  • Male or female patients ≥18 years of age
  • Perianal fistula existing for at least 3 months
  • Perianal fistula that requires an examination under anaesthesia (EUA)
  • Women of childbearing potential must agree to use effective contraception (for details see chapter 8.6) for the duration of the trial
  • Women of childbearing potential: A negative pregnancy test before inclusion into the trial is required
  • Simple fistula, the whole fistula system must be accessible by curettage or brushing

• Crohn's disease (CD) patients only:

  • CD diagnosis established for ≥3 months
  • CD in remission (Harvey-Bradshaw Index ≤4)

Exclusion Criteria:

• All patients:

  • More than 2 external fistula openings
  • History of irradiation of the anorectum
  • Acute perianal abscess.
  • Perianal operation during the last 4 weeks.
  • Known allergy or non-tolerance against either acetylcysteine, doxycycline, Evicel®, metronidazole or ciprofloxacin.
  • Current antibiotic therapy
  • Severe uncontrolled additional medical, surgical or psychiatric condition, requiring active management
  • Current enrollment into a clinical trial interfering with the endpoints or enrollment in another study for treatment of perianal fistula during the last 4 weeks
  • Inability to follow the procedures of the study, e.g. due to language problems, psychiatrical disorders, dementia, etc. of the participant,
  • Previous enrollment into the current study
  • Women who are pregnant or breastfeeding
  • Intention to become pregnant during the course of the study
  • Large pocket (≥ 1cm) within fistula tract
  • Horseshoe shape of the fistula tract
  • Superficial fistula according to clinical examination and/or ultrasound: (Male patients: Fistula tract involves less than 30% of anal sphincter apparatus, Female patients: Fistula tract involves less than 10% of anal sphincter apparatus)

• Crohn's disease patients only:

  • Evidence of active inflammation in the rectum (besides the fistula)
  • Systemic intake of steroid-medication (currently or during the last 4 weeks) in a dose of >20mg prednisone or equivalent
  • New immunosuppressant medication for Crohn's disease within the last 4 weeks before inclusion into the study (changes in 5-ASA medication or rectal treatment with 5-ASA or budesonide are permitted)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Crohn's Disease; 20 patients with Crohn's Disease. Intervention: Fistulodesis	Procedure: Fistulodesis; Fistulodesis comprises the following treatment steps: Curettage and/or brushing of the fistula tract; Mini-excision of the inner (endoanal) fistula opening; Flushing of fistula tract with acetylcysteine (Concentration: 100mg/ml, max. dosage: 20ml); Flushing/ filling of fistula tract with doxycycline (Concentration: 20mg/ml, max. dosage: 10ml); Filling the fistula tract with fibrin-glue (Evicel®). The maximum amount of Evicel® injected will be 20 ml of the combined product.; Surgical closure of inner (endoanal) fistula opening using a Z-suture (Vicryl 3.0); Surgical closure of the outer fistula opening using a Z-suture (Vicryl 3.0) Metronidazole and ciprofloxacin will be used at 500mg two times per day for 10 days after the intervention (baseline).; Other Names: Metronidazole; Ciprofloxacin; Acetylcystein; Doxycycline; Evicel®
Experimental: Patients without IBD; 20 patients without underlying Inflammatory Bowel Disease. Intervention: Fistulodesis	Procedure: Fistulodesis; Fistulodesis comprises the following treatment steps: Curettage and/or brushing of the fistula tract; Mini-excision of the inner (endoanal) fistula opening; Flushing of fistula tract with acetylcysteine (Concentration: 100mg/ml, max. dosage: 20ml); Flushing/ filling of fistula tract with doxycycline (Concentration: 20mg/ml, max. dosage: 10ml); Filling the fistula tract with fibrin-glue (Evicel®). The maximum amount of Evicel® injected will be 20 ml of the combined product.; Surgical closure of inner (endoanal) fistula opening using a Z-suture (Vicryl 3.0); Surgical closure of the outer fistula opening using a Z-suture (Vicryl 3.0) Metronidazole and ciprofloxacin will be used at 500mg two times per day for 10 days after the intervention (baseline).; Other Names: Metronidazole; Ciprofloxacin; Acetylcystein; Doxycycline; Evicel®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fistulodesis success criteria	Closure of all perianal fistula tracts of a patient at week 24 as defined by the presence of all of the following "Fistulodesis success criteria": No secretion from fistula during the last 2 weeks as reported by the patient; No secretion upon careful pressing onto fistula tract; Fistula tract outer opening macroscopically closed upon inspection; No pain at the site of the former fistula opening during gentle pressing	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of quality of life	Improvement of quality of life (IBD-Q) at week 24 compared to baseline	at week 24
Improvement of PDAI	Improvement of PDAI (Peranal Disease Activity Index) at week 4, 12, 24 compared to baseline	at week 4, 12, 24
Reduction in fistula activity	Reduction in fistula activity assessed by fistula drainage assessment (FDA) and "Fistulodesis success criteria" at week 4, 12 and 24 compared to baseline	at week 4, 12 and 24
Risk factors for treatment failure	Risk factors for treatment failure (multivariate analysis)	at week 24
Comparison of fistula closure rates in patients with CD and patients without IBD	Comparison of fistula closure rates in patients with CD and patients without IBD	at week 24
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	at weeks 4, 12, 24, 12 months and 24 months
Long-term follow-up	Long-term follow-up (12 months, 24 months after the end of the study): Assessment of the long-term success after 12 and 24 months by telephone. The patients will be asked about possible fistula symptoms (pain, drainage).	at 12 months and 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota composition of fistula tract	We will analyze the curettage material from the fistula tract by 16S sequencing to determine microbiota composition. We will compare bacterial diversity (number bacterial species) from CD patients and patients without Crohn's disease	material obtained at baseline

Collaborators and Investigators

• Sponsor: University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2017
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: July 10, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 26, 2017

Study Record Updates

• Last Update Posted (Actual): October 26, 2017
• Last Update Submitted That Met QC Criteria: October 25, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Pathological Conditions, Anatomical; Rectal Diseases; Inflammatory Bowel Diseases; Intestinal Fistula; Digestive System Fistula; Fistula; Crohn Disease; Rectal Fistula; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Cytochrome P-450 CYP1A2 Inhibitors; Metronidazole; Doxycycline; Ciprofloxacin
• Other Study ID Numbers: BASEC 2016-01310

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No