Effect of Additional Topical Diltiazem on Botulinum Toxin Injection for Chronic Anal Fissure

Completed

• Conditions: Anal Fissure Chronic
• Interventions: Drug: Botulinum Toxin Type A Injection [Botox]; Drug: Botulinum Toxin Type A Injection [Botox] + Diltiazem Hydrochloride 20 Mg/G Rectal Gel

• Registration Number: NCT05797220
• Lead Sponsor: Istanbul Medipol University Hospital

Brief Summary

Anal fissure (AF) is a painful tear extending from the anal canal to the dentate line. Although the exact pathophysiology is not known, an increase in anal tonus, decreased ano-dermal blood flow and local ischemia are possible mechanisms. The most effective treatment modality in chronic AF is lateral internal sphincterotomy however, incontinence rates are still reported as high as 8-30%. Topical diltiazem and botulinum toxin (BT) injection are good alternatives to surgery with lack of persistent side effects, easy applicability, and reproducibility, however, recurrence rates were reported up to 50% for each. A combination of BT with topical diltiazem may provide better results in terms of healing and recurrence. In this retrospective analysis a comparison of BT injection alone and BT injection combined with topical diltiazem treatment was performed.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-04
• Primary Completion: 2020-06-30
• Study Completion: 2022-06-30
• Status Verified: 2022-10
• Study First Submitted: 2022-10-04
• Study First Submitted QC: 2023-04-03
• Last Update Submitted: 2023-04-03
• Study First Posted: 2023-04-04
• Last Update Posted: 2023-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 217

Inclusion Criteria

• Patients with complaints longer than 8 weeks (chronic anal fissure)
• Patients who completed 24 months of follow-up (3rd day, 10th day, and 2nd-month face-to-face clinic visits and 6, 12, and 24 months phone calls)
• Patients who received conservative treatments including topical diltiazem and nitrites

Exclusion Criteria

• Patients with previous anal surgery (lateral internal sphincterotomy, hemorrhoidectomy, anal fistula)
• Patients with inflammatory bowel diseases
• Patients with accompanying anorectal disease (hemorrhoids, anal fistula, abscess)
• Patients who underwent botulinum toxin injection within 1 year before recruitment
• Patients with anterior, lateral, or multiple fissures
• Comorbidities (AIDS, sexually transmitted disease, tuberculosis, leukemia)
• Pregnancy
• Prescription of calcium canal blockers or nitrites
• Hypersensitivity to diltiazem or botulinum toxin
• Patients without anal pain

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Botulinum toxin group	Botulinum Toxin Type A Injection [Botox]	The procedures were performed at outpatient clinic without anesthesia. Lyophilized 100 IU BT Type-A (BOTOX, Alergan, CA, USA) was applied after diluted with 1 cc saline. A 26-G injector was used to inject 25 unit toxin in every 4 quadrants, to the alignment of clock 12, 3, 6, and 9 to internal anal sphincters.
Botulinum toxin plus topical diltiazem group	Botulinum Toxin Type A Injection [Botox] + Diltiazem Hydrochloride 20 Mg/G Rectal Gel	The procedures were performed at outpatient clinic without anesthesia. Lyophilized 100 IU BT Type-A (BOTOX, Alergan, CA, USA) was applied after diluted with 1 cc saline. A 26-G injector was used to inject 25 unit toxin in every 4 quadrants, to the alignment of clock 12, 3, 6, and 9 to internal anal sphincters. After BT injection, topical 2% diltiazem gel was prescribed, applied 2 times per day for 10 days (2 doses of 1 gr each per day). No selection criteria were used when recommending this treatment; it was randomly suggested to some for a while during the cohort since the surgeon believed it might enhance the efficacy of BT.

Primary Outcome Measures

Name	Time	Method
Fissure healing at 1 month	1 month	Evaluation of complete epithelization of the fissure by the principal investigator by rectal examination
Days to pain-free defecation	1 month	Patient reported time until pain-free defecation. This will be evaluated on 3rd day, 10th day and 1-month outpatient visits.

Secondary Outcome Measures

Name	Time	Method
Complete healing at 48 months	48 months	Any recurrent symptoms evaluated by the surgeon within 2 months in the outpatient clinic and reported by the patient at phone call follow-up at 6 months, 12 months, 24 months, and 48 months.

Trial Locations

Locations (1)

Istanbul Medipol University; 🇹🇷 Istanbul, Other (Non U.s.), Turkey