Clinical trial NCT02158013: Treatment Of Chronic Anal Fissure
Official title: Treatment Of Chronic Anal Fissure (TOCA): a Randomized Clinical Trial on Levorag® Emulgel Versus Diltiazem Gel 2%
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Chronic Anal Fissure
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: Sacomed
First posted: 2014-06-06
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the effect of Levorag Emulgel compared with diltiazem gel on the healing of chronic anal fissures.

Detailed description: Anal fissure is an ulcer-like, longitudinal tear in the anal canal, most commonly located in the dorsal or ventral midline, and distal to the dentate line. Anal fissures constitute a common medical problem that affects sexes equally. The initiation of the fissure is most likely caused by the passage of hard stools that traumatizes the anal canal. Patients suffer from anal pain lasting up to several hours after defecation and rectal bleeding.3 Most acute anal fissures heal spontaneously, but a proportion progress into chronic fissures with symptoms beyond 8-12 weeks. There is no strict definition of a chronic anal fissure, but previously the presence of two of the following three symptoms has been used:

1. Pain after defecation lasting for more than three months;
2. presence of a sentinel anal tag; and
3. Exposure of the horizontal fibres of the internal anal sphincter. The severe pain may be caused by a hypertonic contraction of the internal anal sphincter leading to ischemia. Treatment strategies have therefore aimed to relieve this hypertonia by surgical and non-operative approaches. Primary therapy is initiated with ointments such as Diltiazem and glyceryltrinitrat gels.

A novel approach is the Levorag® Emulgel, an ointment classified as Medical Device class 1. According to the manufacturer (THD SpA, Italy) the effect of Levorag® Emulgel is mediated through the effects of myoxinol, a plant extract from the Hibiscus plant with a botox-like effects on the anal sphincter and carboxymethyl glucan, a natural yeast polysaccharide with immune stimulating properties. The effect of the widely used Diltiazem gel, is mediated through diltiazem hydrochloride, a calcium channel blocker that decreases the anal sphincter pressure.

This is an interventional, randomized clinical trial including adult patients with chronic anal fissures referred directly to the Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, or referred to a private surgical practice in Copenhagen. Patients are randomized to 1) Diltiazem gel 2%, one application twice daily for 8 weeks, or 2) Levorag® Emulgel, one application twice daily for 8 weeks. In addition to the allocated treatment, all patients will be kept on standard care for anal fissure, including high-fibre diet proper hydration and laxatives.

The primary endpoint is the rate of complete healing after 12 weeks. Secondary endpoints are complete healing after 8 weeks, incidence of adverse effects and efficacy on pain relief.

Eligibility criteria: Inclusion Criteria:

1. Danish citizens, age ≥ 18 years
2. Presence of a midline anal fissure, dorsal or ventral
3. Pain during and after defecation lasting for more than 8 weeks
4. Presence of a sentinel anal tag or hypertrophic papilla
5. Exposure of the horizontal fibres of the internal anal sphincter

1-3 has to be fulfilled for inclusion. Additionally 4 AND/OR 5 has to be present

Exclusion Criteria:

1. Inflammatory bowel disease, known venereal disease, immunodeficiency disease
2. Anal/perianal abscess
3. Anal or rectal surgery within 12 weeks
4. Pregnancy or breastfeeding females
5. History of migraine or chronic headache requiring treatment with analgetics
6. Any cardiovascular or cerebrovascular disease
7. Current use of calcium channel blockers in general or history of use of calcium channel blockers in the treatment of the fissure
8. Signs of other rectal diseases, fistula, infection including severe perianal eczema and tumours

Primary outcomes:
measure: Complete healing at week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Complete healing at week 8
timeFrame: 8 weeks
measure: Defecation pain at day 3
timeFrame: 3 days
measure: Defecation pain at day 7
timeFrame: 7 days
measure: Adverse events
timeFrame: 12 weeks
Other outcomes:
measure: Incontinence
timeFrame: 8 and 12 weeks
measure: Anal resting pressure
timeFrame: 8 and 12 weeks
Locations:
city: Aarhus
country: Denmark
facility: Department of Surgery P, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Digestive Disease Center, Bispebjerg Hospital
Study officials:
affiliation: Bispebjerg Hospital
name: Peter-Martin Krarup, MD
role: STUDY_CHAIR
affiliation: Bispebjerg Hospital
name: Andreas Nordholm-Carstensen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nordholm-Carstensen A, Perregaard H, Wahlstrom KL, Hagen KB, Hougaard HT, Krarup PM. Treatment of chronic anal fissure: a feasibility study on Levorag(R) Emulgel versus Diltiazem gel 2. Int J Colorectal Dis. 2020 Apr;35(4):615-621. doi: 10.1007/s00384-020-03515-z. Epub 2020 Jan 24.