Fissure in AnoPhase 4NCT03855046
Complex Treatment of a Chronic Anal Fissure
A Phase 4 study testing IncobotulinumtoxinA 50 U Intramuscular Powder for Solution and Lateral subcutaneous sphincterotomy. in people with Fissure in Ano, run by State Scientific Centre of Coloproctology, Russian Federation at 7 sites in Russia.
Trial summary
This study is aimed at studying the efficacy and safety of treating chronic anal fissure with botulinum toxin versus lateral subcutaneous sphincterotomy. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Fissure in Ano
- What is being tested?
- IncobotulinumtoxinA 50 U Intramuscular Powder for Solution and Lateral subcutaneous sphincterotomy.
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 340 participants
- Where
- 7 sitesRussia
- Study dates
- 1 Sep 2019to 1 Nov 2022
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with chronic anal fissure
Who cannot join
- 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
Show all 10Show fewer
- Pregnancy and lactation
- Individual intolerance and hypersensitivity to botulinum toxin
- Myasthenia gravis and myasthenia-like syndromes
- Anal sphincter insufficiency
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
Russia7 sites, 7 recruiting
- Recruiting
Astrakhan State Medical University
Astrakhan
Kostenko N Vladimirovich, MD, +79880784451 ext. +79880784451, kostenki@mail.ru
- Recruiting
Medical Center ON-CLINIC
Moscow, 119034
Evgeny A Zagryadsky, phd, +79104341786
- Recruiting
SSCCRussia
Moscow, 123423
Sergey A Frolov, phd, +79039689739 ext. 89039689739, DrZharkow@mail.ru
Evgeny E Zharkov, 89039689739 ext. 89039689739, drzharkov@mail.ru
- Recruiting
City Clinical Hospital №24, Department of Health City of Moscow
Moscow
Makoev S Nikolaevich, MD, +79037983363 ext. +79037983363, makoev1972@mail.ru
- Recruiting
GBUZ MO "Lvovskaia Raionaia Bolnica"
Podolsk, Moscow Oblast, 142155
Vladimir Medvedev, MD, +79258977708, mr.vladimirmedvedev@mail.ru
- Recruiting
St. Petersburg State Pavlov Medical University
Saint Petersburg
Demin A Nikolaevich, MD, 89213374143 ext. 89213374143, dan-7691@mail.ru
- Recruiting
Siberian State Medical University
Tomsk
Klinovitskiy I Yurjevich, MD, +79039131776 ext. +79039131776, klinovitskiy@mail.ru
About this study
Official title: A Comparative Efficacy and Safety Study of Lateral Subcutaneous Sphincterotomy and Botulinum Toxin Type A in the Treatment of Chronic Anal Fissure
This study is aimed at studying the efficacy and safety of treating chronic anal fissure with botulinum toxin versus lateral subcutaneous sphincterotomy.
Read the detailed 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).
- Conditions
- Fissure in Ano
- Being tested
- IncobotulinumtoxinA 50 U Intramuscular Powder for Solution, Lateral subcutaneous sphincterotomy.
- Keywords
- 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
- Medical subject headings
- Fissure in Ano, Fecal Incontinence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IncobotulinumtoxinA 50 U Intramuscular Powder for SolutionDrug
Also called Xeomin
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.
Lateral subcutaneous sphincterotomy.Procedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Xeomin | Experimental | 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). Receives: Drug: IncobotulinumtoxinA 50 U Intramuscular Powder for Solution |
| Xeomin control | Active comparator | Complex treatment of chronic anal fissure with lateral subcutaneous sphincterotomy. Receives: Procedure: Lateral subcutaneous sphincterotomy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 60 days
Secondary outcomes (5)
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).
Measured: On day 7, 30 and 60
Non-Healing Wound
Frequency of post-operative wound epithelialization
Measured: On day 60
Profilometry /sphincterometry findings
Internal sphincter spasm or local internal sphincter spasm by the data of anorectal profilometry / or anorectal sphincterometry
Measured: On day 30 and 60
Temporary disability
Duration of temporary disability
Measured: Up to 60 days
Relap
Frequency of relapses
Measured: Up to 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2019
- Study start1 Sep 2019
- Primary completion1 Sep 2022 (estimated)
- Study completion1 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Fissure in AnoStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 340 participants (estimated)
Sponsor and investigators
- Lead sponsor
- State Scientific Centre of Coloproctology, Russian Federation
- Sponsor type
- Other government
- Collaborators
- St. Petersburg State Pavlov Medical University, Astrakhan State Medical University, Siberian State Medical University, City Clinical Hospital №24, Department of Health City of Moscow, GBUZ MO "Lvovskaia Raionaia Bolnica", Medical Center ON-CLINIC
- Responsible party
- Sponsor
- Investigators
- Sergey A. Frolov, Ph.D., Principal investigator, State Scientific Centre of Coloproctology, Russian Federation (SSCCRussia)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03855046
- Sponsor's protocol ID
- 56IG701SSCC978
- Status last verified
- Jan 2022
- First submitted
- 25 Feb 2019
- Last updated
- 27 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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. doi: 10.1097/DCR.0000000000000735. No abstract available.
PubMed 27926552Sohn 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. doi: 10.1007/BF02048108.
PubMed 1582352Renzi 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. doi: 10.1007/s10350-007-9162-7. Epub 2007 Dec 15.
PubMed 18080713Gui 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. doi: 10.1016/s0140-6736(94)90633-5.
PubMed 7934496Khan 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
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.
PubMed 27539490Nasr 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.
PubMed 20703472Valizadeh 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.
PubMed 22430300Magdy 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. doi: 10.1007/s11605-012-1984-5. Epub 2012 Aug 7.
PubMed 22869534Katsinelos 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. doi: 10.1007/s00384-005-0766-x. Epub 2005 Aug 10.
PubMed 16091912Chen 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.
PubMed 24500725Bagrasaryan LS, Surgical treatment of anal fissure with anal sphincter pneumodivulsion. 2010: p. 115
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. doi: 10.1007/BF02047871.
PubMed 1511644Hyman N. Incontinence after lateral internal sphincterotomy: a prospective study and quality of life assessment. Dis Colon Rectum. 2004 Jan;47(1):35-8. doi: 10.1007/s10350-003-0002-0. Epub 2004 Jan 14.
PubMed 14719148Sultan 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. doi: 10.1056/NEJM199312233292601.
PubMed 8247054