Comparative Evaluation of MEBO Ointment and Topical Diltiazem Ointment in the Treatment of Acute Anal Fissure

NCT04153032 | Recruiting Phase 2 DMC

• 1 other identifier: BIO-2018-0547
• Study Type: interventional
• Target: 183
• Locations: 1 country
• Sites: 1

Brief Summary

No study to date has compared topical DTZ to MEBO ointment in the treatment of anal fissure. Therefore, the present study aims to compare the efficacy and safety of DTZ to MEBO in the treatment of acute anal fissure. The investigators propose to conduct a comparative randomized clinical study. In this study, the investigators will compare patients with acute anal fissure receiving MEBO ointment vs Topical DTZ ointment vs a combination of MEBO and DTZ ointment. Hypothesis: MEBO in combination with DTZ is more effective than DTZ or MEBO alone in the treatment of acute anal fissure.

Conditions

Anal Fissure

Keywords

Anal fissure; MEBO; topical diltiazem; MEBO/Diltiazem combination

Outcome Measures

Primary Outcomes (2)

• Change in Pain Score

  Pain is evaluated through the Numerical Rating Scale, range 0-10 where 0 = no pain and 10 = worst pain imaginable

  Baseline to 1 week from the start date of the study

• Wound Healing

  Wound healing is assessed through physical examination: digital rectal examination is not done in case of painful anal fissure. Assessment for wound healing will be performed by the treating physician of the patient. The patient will be asked to strain to make the anal fissure more visible. If it is difficult to see on physical examination, digital rectal exam is done carefully. The degree of healing will be reported as none, partial or complete.

  At 1 week from that start date of the study

Secondary Outcomes (4)

• Change in Pain Score

  At 6 and 10 weeks from the start date of the study

• Wound Healing

  At 6 and 10 weeks from the start date of the study

• Defecation Strain Score

  At 1 week, 6 weeks, and 10 weeks from that start date of the study

• Global Impression of Improvement

  At 1 week, 6 weeks, and 10 weeks from that start date of the study

Other Outcomes (1)

• Incidence of Treatment-Related Adverse Events

  At 1 week, 6 weeks, and 10 weeks from that start date of the study

Study Arms (3)

DTZ arm

EXPERIMENTAL

The first group of patients will apply MEBO ointment peri-anally 3 times daily for 6 weeks.

Drug: Mebo

MEBO arm

EXPERIMENTAL

The second group of patients will apply topical DTZ ointment peri-anally 3 times daily for 6 weeks.

Drug: Diltiazem

MEBO and DTZ arm

EXPERIMENTAL

The third group will apply a combination of MEBO and DTZ ointment peri-anally 3 times daily for 6 weeks. Those who fail therapy (meaning they report no pain improvement after two weeks of treatment) from either the MEBO or the Diltiazem arm will be switched to the combination arm. If they also fail to improve after two weeks on the treatment arm, then they will be offered surgery. If the patient refuses to switch to the combination arm and wishes to proceed to surgery immediately, then the patient will be directed to surgery.

Drug: Diltiazem; Drug: Mebo

Interventions

Diltiazem DRUG

DTZ is a calcium channel blocker for the treatment of chronic anal fissure

Also known as: DTZ

MEBO and DTZ arm; MEBO arm

Mebo DRUG

Moist exposed burn ointment (MEBO) is a tropical Chinese medicine composed of sesame oil and herbal plants that is clinically used for the treatment of burn wound.

DTZ arm; MEBO and DTZ arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be 18 years and above.
• Subjects with 3 months (90 days) or less history of painful anal fissure (AF), prior to screening, where AF-related pain-associated with, or following, defecation is experienced at least twice a week during the symptomatic phase, with pain scores at an average of ≥ 3 on an 11-point NRS (Numerical Rating Scale, range 0-10 where 0 = no pain and 10 = worst pain imaginable).
• Subjects with an average of ≥4 on an 11-point NRS during the screening phase for worst anal pain associated with, or following, defecation for the most recent 3 days on which the subject has defecated.
• Subjects with evidence of a radial fissure, with induration at the edges, seen on anal examination.
• Willing to stop all other concomitant topical preparations applied perianally prior to commencing study treatment, and throughout the study. There will be a "washout" period of at least 2 weeks prior to commencing the study for subjects who were using other concomitant topical preparations applied perianally.
• Able to give consent

You may not qualify if:

• Subjects unwilling to be examined for AF.
• Subjects who have undergone the following procedures:
• Lateral sphincterotomy or anal stretch or other previous surgery involving the anal canal or perianal region (hemorrhoidectomy, anal fistula surgery).
• Incision of perianal abcess.
• Subjects who have had sub-fissure injection of botulinum toxin within 6 months period prior to screening, or have used glyceryl trinitrate (GTN) ointment for \>1 week in the 4 weeks prior to the screening visit.
• Subjects with AF associated with other conditions (drug-induced \[e.g. nicorandil\], trauma, HIV infection, fistula-in-ano, inflammatory bowel disease, perianal sepsis or malignancy).
• Subjects with cardiovascular disease
• Subjects with known hypersensitivity to DTZ or the ingredients of MEBO (Sesame oil)
• Subjects taking medications prohibited by the protocol.
• Subjects who have taken experimental agents must have been discontinued at least 8 weeks prior to screening, or for a period equivalent to 5 half-lives (t1/2) of the agents.
• Subjects who have the following gastrointestinal disorders:
• Inflammatory bowel disease.
• Chronic faecal incontinence.
• History of radiation therapy to the pelvis.
• Fixed anal stenosis/fibrosis.

Sponsors & Collaborators

• American University of Beirut Medical Center: lead

Study Sites (1)

American University of Beirut

Beirut, Lebanon

RECRUITING

Related Publications (24)

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  BACKGROUND

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• Hirsch T, Ashkar W, Schumacher O, Steinstraesser L, Ingianni G, Cedidi CC. Moist Exposed Burn Ointment (MEBO) in partial thickness burns - a randomized, comparative open mono-center study on the efficacy of dermaheal (MEBO) ointment on thermal 2nd degree burns compared to conventional therapy. Eur J Med Res. 2008 Nov 24;13(11):505-10.

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• Ang ES, Lee ST, Gan CS, See P, Chan YH, Ng LH, Machin D. The role of alternative therapy in the management of partial thickness burns of the face--experience with the use of moist exposed burn ointment (MEBO) compared with silver sulphadiazine. Ann Acad Med Singap. 2000 Jan;29(1):7-10.

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• National Institute for Health and Care Excellence. Chronic anal fissure: 2% topical diltiazem hydrochloride. Evidence Summary. Manchester: 2013.

  BACKGROUND

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  PMID: 23204700 BACKGROUND

• Tsunoda A, Kashiwagura Y, Hirose K, Sasaki T, Kano N. Quality of life in patients with chronic anal fissure after topical treatment with diltiazem. World J Gastrointest Surg. 2012 Nov 27;4(11):251-5. doi: 10.4240/wjgs.v4.i11.251.

  PMID: 23494072 BACKGROUND

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• Guo-Lin H, Zhong-shen L. Experience with MEBO in Treating 42 Cases of Anal Fissure. The Chinese Journal of Burns Wounds and Surface Ulcers. 2001(2).

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  PMID: 20013110 BACKGROUND

• El Charif MH, Doughan S, Kredly R, Kassas S, Azab R, Sbaity E. MEBO versus topical Diltiazem versus a combination of both ointments in the treatment of acute anal fissure: a randomized clinical trial protocol. BMC Complement Med Ther. 2021 Feb 24;21(1):75. doi: 10.1186/s12906-021-03227-z.

  PMID: 33627111 DERIVED

MeSH Terms

Conditions

Fissure in Ano

Interventions

Diltiazem

Condition Hierarchy (Ancestors)

Anus Diseases; Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Eman Sbaity, MD

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eman Sbaity, MD

CONTACT

+961-76-110882; es25@aub.edu.lb

Mohamad Hadi El Charif, MD

CONTACT

+961-3-771917; mohamadhadi.elcharif@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The physician and the patient will not be blinded to the allocation, but the rest of the study team will be blinded. We will blind to allocation the physician who will assess for outcomes, and the research assistants who are collecting the data, data analysts.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor of Surgery

Model Details: 1:1:1 randomized, controlled, parallel design

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: November 6, 2019
• Study Start: December 1, 2019
• Primary Completion: January 1, 2026
• Study Completion: January 30, 2026
• Last Updated: January 29, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)