The use of a methylene blue and glyceryl trinitrate-based cream for the treatment of chronic anal fissures: a phase II randomized pilot trial from a referral coloproctological unit

Tech Coloproctol. 2025 Jan 3;29(1):39. doi: 10.1007/s10151-024-03029-8.

Abstract

Background: Chronic anal fissures (CAFs) are the second most common anorectal disease. Non-surgical treatment includes several options with controversial efficacy. The aim of this study was to evaluate the efficacy and safety of a new ointment based on methylene blue in addition to glyceryl trinitrate.

Methods: A phase II randomized single-centre triple-blinded study was carried out in a tertiary proctology unit on patients with CAF. The enrollment started after local ethics committee approval (study n. 6461, protocol approval n. 0045085). Eligible consecutive patients were randomized to one of three different groups, each receiving a different ointment. The efficacy of the treatment was evaluated with the REALISE score.

Results: Nine patients were treated with cream A (median age 47 years, IQR 40-56, 22% female), nine with cream B (median age 52 years, IQR 49-57, 33% female), and nine with cream C (median age 58 years, IQR 46-62, 55% female). In group A, REALISE scores decreased significantly from a median of 22 (IQR 12-25) to 6 (IQR 4-8) (p < 0.05) after 40 days. In group B, REALISE scores improved significantly from a median of 20 (IQR 17-22) to 5 (IQR 4-9) (p < 0.05). In group C, REALISE scores decreased significantly from a median of 19 (IQR 19-20) to 4 (4-5) (p < 0.05). No statistically differences were recorded. The healing rate was 77% with creams A and C, while it was 44% with cream B.

Conclusion: Methylene blue-based ointments could be a new and innovative treatment for the non-operative management and healing of CAFs.

Keywords: Anal fissure; Anal pain; Blue cream; Glyceryl trinitrate; Methylene blue; REALISE scoring system.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • Administration, Topical
  • Adult
  • Chronic Disease
  • Drug Therapy, Combination
  • Female
  • Fissure in Ano* / drug therapy
  • Fissure in Ano* / therapy
  • Humans
  • Male
  • Methylene Blue* / administration & dosage
  • Methylene Blue* / therapeutic use
  • Middle Aged
  • Nitroglycerin* / administration & dosage
  • Nitroglycerin* / therapeutic use
  • Ointments*
  • Pilot Projects
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / therapeutic use

Substances

  • Methylene Blue
  • Nitroglycerin
  • Ointments
  • Vasodilator Agents