Clinical trial NCT03322488: Fistulodesis Pilot Study for Closure of Perianal Fistulae
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Perianal Fistula
Crohn Disease
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2017-10-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 20 patients with Crohn's disease and 20 patients without Crohn's disease will be recruited
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Fistulodesis success criteria
timeFrame: week 24
Secondary outcomes:
measure: Improvement of quality of life
timeFrame: at week 24
measure: Improvement of PDAI
timeFrame: at week 4, 12, 24
measure: Reduction in fistula activity
timeFrame: at week 4, 12 and 24
measure: Risk factors for treatment failure
timeFrame: at week 24
measure: Comparison of fistula closure rates in patients with CD and patients without IBD
timeFrame: at week 24
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: at weeks 4, 12, 24, 12 months and 24 months
measure: Long-term follow-up
timeFrame: at 12 months and 24 months
Other outcomes:
measure: Microbiota composition of fistula tract
timeFrame: material obtained at baseline
Locations:
city: Zurich
country: Switzerland
facility: Division of Gastroenterology, University Hospital Zurich
city: Zürich
country: Switzerland
facility: Bethanien-Klinik
Study officials:
References: