Complex Treatment of a Chronic Anal Fissure

Fissure in Ano Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03855046
• Other study ID #: 56IG701SSCC978
• Status: Recruiting
• Phase: Phase 4
• Start date: September 1, 2019
• Est. completion date: November 1, 2022

Study information

• Verified date: January 2022
• Source: State Scientific Centre of Coloproctology, Russian Federation
• Contact: Evgeny E. Zharkov, MD
• Phone: 89039689739
• Email: drzharkov[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: November 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Fissure in Ano

Intervention

Drug:
• IncobotulinumtoxinA 50 U Intramuscular Powder for Solution
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.

Procedure:
• Lateral subcutaneous sphincterotomy.
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.

Locations

Country	Name	City	State
Russian Federation	Astrakhan State Medical University	Astrakhan
Russian Federation	City Clinical Hospital ?24, Department of Health City of Moscow	Moscow
Russian Federation	Medical Center ON-CLINIC	Moscow
Russian Federation	SSCCRussia	Moscow
Russian Federation	GBUZ MO "Lvovskaia Raionaia Bolnica"	Podolsk	MO
Russian Federation	St. Petersburg State Pavlov Medical University	St. Petersburg
Russian Federation	Siberian State Medical University	Tomsk

Sponsors (7)

Lead Sponsor	Collaborator
State Scientific Centre of Coloproctology, Russian Federation	Astrakhan State Medical University, City Clinical Hospital ?24, Department of Health City of Moscow, GBUZ MO "Lvovskaia Raionaia Bolnica", Medical Center ON-CLINIC, Siberian State Medical University, St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

References & Publications (24)

Bagrasaryan LS, Surgical treatment of anal fissure with anal sphincter pneumodivulsion. 2010: p. 115

Bobkiewicz A, Francuzik W, Krokowicz L, Studniarek A, Ledwosinski W, Paszkowski J, Drews M, Banasiewicz T. Botulinum Toxin Injection for Treatment of Chronic Anal Fissure: Is There Any Dose-Dependent Efficiency? A Meta-Analysis. World J Surg. 2016 Dec;40(12):3064-3072. doi: 10.1007/s00268-016-3693-9. Review. Erratum in: World J Surg. 2016 Dec;40(12 ):3063. — View Citation

Chen HL, Woo XB, Wang HS, Lin YJ, Luo HX, Chen YH, Chen CQ, Peng JS. Botulinum toxin injection versus lateral internal sphincterotomy for chronic anal fissure: a meta-analysis of randomized control trials. Tech Coloproctol. 2014 Aug;18(8):693-8. doi: 10.1007/s10151-014-1121-4. Epub 2014 Feb 6. Review. — View Citation

Delechenaut P, Leroi AM, Weber J, Touchais JY, Czernichow P, Denis P. Relationship between clinical symptoms of anal incontinence and the results of anorectal manometry. Dis Colon Rectum. 1992 Sep;35(9):847-9. — View Citation

Gui D, Cassetta E, Anastasio G, Bentivoglio AR, Maria G, Albanese A. Botulinum toxin for chronic anal fissure. Lancet. 1994 Oct 22;344(8930):1127-8. — View Citation

Hyman N. Incontinence after lateral internal sphincterotomy: a prospective study and quality of life assessment. Dis Colon Rectum. 2004 Jan;47(1):35-8. Epub 2004 Jan 14. — View Citation

Iswariah H, Stephens J, Rieger N, Rodda D, Hewett P. Randomized prospective controlled trial of lateral internal sphincterotomy versus injection of botulinum toxin for the treatment of idiopathic fissure in ano. ANZ J Surg. 2005 Jul;75(7):553-5. — View Citation

Jorge JM, Wexner SD. Anorectal manometry: techniques and clinical applications. South Med J. 1993 Aug;86(8):924-31. — View Citation

Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum. 1993 Jan;36(1):77-97. Review. — View Citation

Katsinelos P, Papaziogas B, Koutelidakis I, Paroutoglou G, Dimiropoulos S, Souparis A, Atmatzidis K. Topical 0.5% nifedipine vs. lateral internal sphincterotomy for the treatment of chronic anal fissure: long-term follow-up. Int J Colorectal Dis. 2006 Mar;21(2):179-83. Epub 2005 Aug 10. — View Citation

Khan M.I., Khan H., Khan A.U., et. al. Comparing the efficacy of botulinum toxin injection and lateral internal sphincterotomy for chronic anal fissure. KJMS, 2016. 9(1): p. 6

Khubchandani IT, Reed JF. Sequelae of internal sphincterotomy for chronic fissure in ano. Br J Surg. 1989 May;76(5):431-4. — View Citation

Magdy A, El Nakeeb A, Fouda el Y, Youssef M, Farid M. Comparative study of conventional lateral internal sphincterotomy, V-Y anoplasty, and tailored lateral internal sphincterotomy with V-Y anoplasty in the treatment of chronic anal fissure. J Gastrointest Surg. 2012 Oct;16(10):1955-62. Epub 2012 Aug 7. — View Citation

Nasr M, Ezzat H, Elsebae M. Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a randomized controlled trial. World J Surg. 2010 Nov;34(11):2730-4. doi: 10.1007/s00268-010-0736-5. — View Citation

Nelson RL, Thomas K, Morgan J, Jones A. Non surgical therapy for anal fissure. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD003431. doi: 10.1002/14651858.CD003431.pub3. Review. — View Citation

Renzi A, Izzo D, Di Sarno G, Talento P, Torelli F, Izzo G, Di Martino N. Clinical, manometric, and ultrasonographic results of pneumatic balloon dilatation vs. lateral internal sphincterotomy for chronic anal fissure: a prospective, randomized, controlled trial. Dis Colon Rectum. 2008 Jan;51(1):121-7. Epub 2007 Dec 15. — View Citation

Sohn N, Eisenberg MM, Weinstein MA, Lugo RN, Ader J. Precise anorectal sphincter dilatation--its role in the therapy of anal fissures. Dis Colon Rectum. 1992 Apr;35(4):322-7. — View Citation

Stewart DB Sr, Gaertner W, Glasgow S, Migaly J, Feingold D, Steele SR. Clinical Practice Guideline for the Management of Anal Fissures. Dis Colon Rectum. 2017 Jan;60(1):7-14. — View Citation

Sultan AH, Kamm MA, Hudson CN, Thomas JM, Bartram CI. Anal-sphincter disruption during vaginal delivery. N Engl J Med. 1993 Dec 23;329(26):1905-11. — View Citation

Tjandra JJ, Han WR, Ooi BS, Nagesh A, Thorne M. Faecal incontinence after lateral internal sphincterotomy is often associated with coexisting occult sphincter defects: a study using endoanal ultrasonography. ANZ J Surg. 2001 Oct;71(10):598-602. — View Citation

Valizadeh N, Jalaly NY, Hassanzadeh M, Kamani F, Dadvar Z, Azizi S, Salehimarzijarani B. Botulinum toxin injection versus lateral internal sphincterotomy for the treatment of chronic anal fissure: randomized prospective controlled trial. Langenbecks Arch Surg. 2012 Oct;397(7):1093-8. doi: 10.1007/s00423-012-0948-2. Epub 2012 Mar 20. — View Citation

Zbar A., M. Aslam, and V. Allgar, Faecal incontinence after internal sphincterotomy for anal fissure. Techniques in Coloproctology, 2000. 4(1): p. 25-28.

Zetterström J, Mellgren A, Jensen LL, Wong WD, Kim DG, Lowry AC, Madoff RD, Congilosi SM. Effect of delivery on anal sphincter morphology and function. Dis Colon Rectum. 1999 Oct;42(10):1253-60. — View Citation

Zharkov, EE, Comprehensive treatment of chronic anal fissure. 2009: p. 126.

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Non-Healing Wound	Frequency of post-operative wound epithelialization	On day 60
Secondary	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
Secondary	Temporary disability	Duration of temporary disability	Up to 60 days
Secondary	Relap	Frequency of relapses	Up to 60 days