Complex Treatment of a Chronic Anal Fissure

Study Overview
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Brief Summary
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This study is aimed at studying the efficacy and safety of treating chronic anal fissure with botulinum toxin versus lateral subcutaneous sphincterotomy.

Detailed Description
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Chronic anal fissure is a rupture of anal canal mucosa lasting for more than 2 months and resistant to non-surgical treatment. This condition is attended by severe pain syndrome during and after bowel movement (defecation). This condition is most frequent in younger and working-age adults; therefore, the treatment issue is of particular relevance. The main cause of chronic anal fissure development is spasm of the internal sphincter. It should be eliminated in the first instance, in order to provide the effective therapy. All the main treatment methods, such as medicinal relaxation of the internal sphincter with 0.4% nitroglycerin ointment, lateral subcutaneous sphincterotomy, and pneumodivulsion of the anal sphincter are aimed at its removal. However, the optimal method has not yet been developed. Non-surgical treatments are often attended by relapse of disease, while surgical treatment is often complicated by intestinal contents incontinence, usually gas and loose or hard stool in some occasions (grade 3 anal sphincter insufficiency). In particular, lateral subcutaneous sphincterotomy performed in such patients is associated with an increase in the degree of anal incontinence in the early post-operative period. Botulinum Toxin Type A application in complex treatment of patients with chronic anal fissure (after fissure excision) is intended to improve the therapy results, namely to reduce the frequency and duration of anal sphincter insufficiency after sphincter spasm removal (reduction in the number of patients suffering from post-operative incontinence).

Official Title
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A Comparative Efficacy and Safety Study of Lateral Subcutaneous Sphincterotomy and Botulinum Toxin Type A in the Treatment of Chronic Anal Fissure

Conditions
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Fissure in Ano

Intervention / Treatment
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* Drug: IncobotulinumtoxinA 50 U Intramuscular Powder for Solution
* Procedure: Lateral subcutaneous sphincterotomy.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic anal fissure Exclusion Criteria: Inflammatory diseases of the colon Pectenosis Previous surgical interventions on the anal canal IV grade internal and external hemorrhoids Rectal fistula Severe somatic diseases at the decompensation stage Pregnancy and lactation Individual intolerance and hypersensitivity to botulinum toxin Myasthenia gravis and myasthenia-like syndromes Anal sphincter insufficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: A multicenter, prospective, randomized, controlled clinical study. Surgical removal of anal fissure followed by internal sphincter relaxation with Botulinum toxin type A is performed in the study group. Lateral subcutaneous sphincterotomy to relax sphincter is a method of choice in the control group. Patients are randomized with envelope method
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xeomin<br>Complex treatment of chronic anal fissure with drug-induced relaxation of the internal sphincter with Botulinum Toxin Type A. (IncobotulinumtoxinA 50 U Intramuscular Powder for Solution). | Drug: IncobotulinumtoxinA 50 U Intramuscular Powder for Solution<br>* Sparing surgical removal of fissure without internal sphincter incision is held under spinal anesthesia in surgical room at lithotomy position using electrocoagulation. After that Botulinum Toxin Type A is injected into the internal anal sphincter at 1, 5, 7 and 11 o'clock (localization of injection points), 10 U at each point (40 U in total). Botulinum toxin type A (a 50 U vial) is diluted with 1.0 ml of 0.9% saline solution.<br>* Other names: Xeomin;|
| Active Comparator: Xeomin control<br>Complex treatment of chronic anal fissure with lateral subcutaneous sphincterotomy. | Procedure: Lateral subcutaneous sphincterotomy.<br>* The patient is positioned on the table like for perineal lithotomy. After spinal anesthesia, the anal canal and then the surgical field are treated with 70% ethanol. Under the rectal speculum control, sparing surgical removal of fissure without internal sphincter incision is held using electrocoagulation.Then, in a 3 or 9 o'clock position, a narrow (eye) scalpel is inserted into the intersphincteric groove separating the external and internal sphincters, the scalpel blade is turned to the rectal lumen, and the internal sphincter is dissected up to the wall of the anal canal mucosa under the control of the finger inserted into the anal canal. After controlling hemostasis, the operation is ended with the introduction of the vent tube and hemostatic sponge.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anal sphincter insufficiency | Frequency of anal sphincter insufficiency according to the Wexner scale incontinence after the surgical intervention. Self reported daily meausure outcome, wich evaluate from 0 - to 20 points (where 0 points = full feacal continence; 20 points = full feacal incontinence). | Up to 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-item pain intensity (P2) | Self reported pain intensity after the defecation and during the day after the surgical intervention. Each item is scored 0-10 (0 = no pain; 10 = pain as bad, as can can be). | On day 7, 30 and 60 | 
| Non-Healing Wound | Frequency of post-operative wound epithelialization | On day 60 | 
| Profilometry /sphincterometry findings | Internal sphincter spasm or local internal sphincter spasm by the data of anorectal profilometry / or anorectal sphincterometry | On day 30 and 60 | 
| Temporary disability | Duration of temporary disability | Up to 60 days | 
| Relap | Frequency of relapses | Up to 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Internal sphincterotomy, Anal fissure, Chronic anal fissure, botulinum toxin A, proctologic diseases, surgical treatment, Chronic anal pain, Fecal incontinence, Spasm of the internal sphincter, Anal sphincter insufficiency, randomized