Adipose Tissue Injection for the Treatment of Complex Cryptoglandular Perianal Fistula

Study Overview
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Brief Summary
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The incidence of complex cryptoglandular anal fistula is high, it affects eminently young patients and implies an important alteration in their quality of life and high prevalence in sick leave. Its treatment remains a real challenge due to the limited efficacy of sphincter preservation techniques and the inevitable risk of faecal incontinence in those cases that require surgery. Goals: To evaluate the efficacy and safety of the injection of freshly collected autologous adipose tissue as a minimally invasive, highly reproducible alternative, without risk for the continence of the patient, and of very low cost, in the treatment of complex cryptoglandular anal fistula. Methodology: Prospective multicenter, randomized, double-blinded, parallel-group, placebo-controlled clinical trial. Randomization list for each center to ensure the balance of inter-center allocation. Patients older than 18 years with cryptoglandular anal fistula with suppuration for more than 6 weeks and less than 1 year, who have received at most: curettage and drainage placement will be included. Treatment group: injection of fresh autologous fat into the fistulous tract, after curettage and closure of the internal orifice, and after lipoaspirate fat in the abdomen and centrifugation thereof. Placebo group: curettage and closure of the internal orifice and simulated intervention in the abdomen. Evaluation: protocolized clinical history and fistula complexity score (CFS), subjective perception of its pathology, St.Marks continence score, Quality of life questionnaire (QoLAF), and endoanal 3D ultrasound, at baseline, at one week, and at 3, 6 and 12 months after the intervention. The patients and the evaluator will be blind to the treatment. Patients who cannot end up receiving treatment due to intraoperative incidents or medical decision will be excluded from the study (post randomization exclusion). In each center there will be a blind evaluator to perform the follow-ups and endoanal ultrasound.

Official Title
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Adipose Tissue Injection for the Treatment of Complex Cryptoglandular Perianal Fistula

Conditions
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Anal Fistula

Intervention / Treatment
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* Procedure: Injection of autologous freshly collected adipose tissue
* Procedure: sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years Anal fistula with suppuration for more than 6 weeks and less than 1 year, that have not received any previous treatment or at most: curettage and drainage placement Complex cryptoglandular anal fistula: medium or high transsphincteric fistula, suprasphincteric fistula and extra sphincter fistula, shown by endoanal ultrasound. Low transsphincteric fistulas in patients with fecal incotinence. Any cryptoglandular anal fistula with risk factors for anal incontinence: anterior location fistula in women, history of pelvic surgery (hysterectomy, rectal resection), history of pelvic radiotherapy or previous anal surgery Draining with Seton placed >2 weeks before surgery and present at the time of treatment Disposition and ability to comply with the study protocol Signed informed consent Exclusion Criteria: Patients diagnosed with inflammatory bowel disease Previous history of perianal fistula treated with any surgery different than curettage and seton placement (this include any type of surgery with curative intention, i.e. flap, lift technique, Radiofrequency, laser, stem cells, Filac, etc) Presence of Rectovaginal fistula Technical impossibility for lipoaspirate (liposuction) technique. Presence of perianal collections larger than 2cm Presence of several paths from 1 internal hole only Presence of secondary fistula paths or tracts Perianal surgery necessary at the time of planning the fistula treatment, for reasons other than fistula. Major surgery needed within 28 days of recruitment Immunomodulator treatment or corticotherapy in a previous period of 6 months Stoma patients Serious medical or psychiatric illness that requires frequent hospitalization. Pregnancy, pregnancy plans or breastfeeding in the next 12 months Active smokers, or ex-smokers of less than 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control group<br> | Procedure: sham<br>* curettage and closure of the internal orifice of the anal fistula and simulated intervention in the abdomen.<br>|
| Experimental: Experimental group<br> | Procedure: Injection of autologous freshly collected adipose tissue<br>* injection of fresh autologous fat, previously lipoaspirates from the patient's abdomen and centrifugated, into the fistulous tract, after curettage and closure of the internal opening.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete fistula healing | Comparison of the proportion of cases with complete fistula healing within 24 weeks of the intervention, defined as the absence of drainage through the external orifice, its complete reepithelialization and the absence of collections confirmed by endoanal ultrasound. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's Quality of life | Improvement in quality of life (measured with the Quality of Life in Patients with Anal Fistula Questionnaire, QoLAF). Score from 14 to 70, where 14 means no quality of life alteration and 70 means severe quality of life alteration. | 6 and 12 months after treatment. | 
| Patient's Subjective Perception | Improvement in patient subjective evaluation using a Visual Analogue Scale (VAS). Score from 0 to 10, where 0 means no problem and 10 means severe problem and alteration of my quality of life. | 6 and 12 months after treatment. | 
| Fistula severity | Improvement in fistula severity according to the Complexity Fistula score (CFS). Score from 3 to 15, where 3 means low complexity and 15 means high complexity | 6 and 12 months after treatment. | 
| Adverse events | Evaluation of the safety by the incidence of adverse events and serious adverse events. | 3, 6 and 12 months after treatment. |