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A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in patients with chronic anal fissures
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  1. J H Scholefield1,
  2. J U Bock2,
  3. B Marla3,
  4. H J Richter4,
  5. S Athanasiadis5,
  6. M Pröls6,
  7. A Herold7
  1. 1Division of GI Surgery, University Hospital, Nottingham NG7 2UH, UK
  2. 2Proktologische Praxis, Kiel, Germany
  3. 3Proktologische Praxis, Essen, Germany
  4. 4Proktologische Praxis, Hamburg, Germany
  5. 5St Joseph-Hospital, Duisburg, Germany
  6. 6Dr Falk Pharma, GmbH, Freiburg, Germany
  7. 7Enddarmzentrum Mannheim, Germany
  1. Correspondence to:
    Professor J Scholefield, Division of GI Surgery, University Hospital, Nottingham NG7 2UH, UK;
    john.scholefield{at}nottingham.ac.uk

Abstract

Background: Anal fissure is a common painful condition affecting the anal canal. The majority of acute fissures heal spontaneously. However, some of these acute fissures do not resolve but become chronic. Chronic anal fissures were traditionally treated by anal dilation or by lateral sphincterotomy. However, both of these surgical treatments may cause a degree of incontinence in up to 30% of patients. Several recent trials have shown that nitric oxide donors such as glyceryl trinitrate (GTN) can reduce sphincter pressure and heal up to 70% of chronic fissures.

Aim: This study addressed the dose-response to three different concentrations of GTN ointment compared with placebo in a double blind randomised controlled trial.

Method: A double blind, multicentre, randomised controlled trial was set up to compare placebo ointment against three active treatment arms (0.1%, 0.2%, and 0.4% GTN ointment applied at a dose of 220 mg twice daily) in chronic anal fissures. The primary end point was complete healing of the fissure.

Results: Two hundred patients were recruited over an eight month period from 18 centres. After eight weeks of treatment the healing rate in the placebo group was 37.5% compared with 46.9% for 0.1%, 40.4% for 0.2%, and 54.1% for 0.4% GTN. None was significantly better than the placebo response. A secondary analysis excluded fissures without secondary criteria for chronicity. Healing rates were then found to be 24% in the placebo group compared with 50% in the 0.1% GTN group, 36% in the 0.2% group, and 57% in the 0.4% GTN group. These values were statistically significantly different for the placebo group compared with 0.1% GTN, 0.4% GTN, and for the GTN treated group as a whole.

Conclusions: The results of this study have demonstrated the significant benefit of topical GTN when applied to patients suffering from chronic anal fissures but acute fissures showed a tendency to resolve spontaneously. The high proportion of fissures which healed in the placebo group suggests that the definition of “chronicity” needs to be reassessed. Further studies are required to confirm the optimal therapeutic strategy.

  • anal fissure
  • anus
  • glyceryl trinitrate
  • nitric oxide
  • randomised trial
  • GTN, glyceryl trinitrate
  • MARP, maximal anal resting pressure
  • ITT, intention to treat
  • PP, per protocol

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Footnotes

  • On behalf of the GTN study group (see acknowledgements).

  • Conflict of interest: The authors wish to point out that this study was conducted in a double blind and randomised fashion and was sponsored by Dr Falk Pharma. The data monitoring and data collection was undertaken by an independent commercial group, paid by the sponsors. Tabulation and initial statistical tests were performed by the sponsors and have subsequently been verified and finalised by an independent statistician.

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