A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in patients with chronic anal fissures

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.

Role of 0.4% glyceryl trinitrate ointment after haemorrhoidectomy: results of a prospective randomised study

“…A theory is that GTN may works in the same manner as in anal fissures, increasing the anodermal blood flow. Good wound healing is essential to prevent perianal irritation, discharge and pain, dehiscence, bacterial infection and reactionary bleeding [20]. Similar findings have been reported in several studies done using metronidazole.…”

Comparison of Lateral Internal Sphincterotomy with Topical Nitroglycerine Treatment in Patients with Chronic Anal Fissure: A Prospective Randomised Study

“…Psyllium may have exerted its effect by preventing the formation of hard stool causing mechanical trauma responsible for the development of chronic anal fissure and diarrheal attacks. Recent studies have emphasized that topical nitroglicerin at 0.04% concentration 2×1.5 mg is the most efficient dose in treatment of chronic anal fissure [28,29]. In a study carried out by Ergun et al [30] on 568 pharmacists, it was shown that only 24 (%4) of the pharmacists prepared topical nitroglicerin prescription and %0.4 nitroglicerin content was not found exactly at this ratio in preparations.…”

Anal Fissure Revisited : A Systematic Review

“…In fact, up to 20% of patients cease GTN therapy due to the severity of their headaches. [30], [31], [32], [33] A 2%GTN ointment applied twice to the anoderm for 6 weeks results in a complete healing in 98% of patients. [6] In another study, Topical diltiazem ointment was used as an agent for chemical sphincterotomy for chronic anal fissure.…”