A randomised, prospective, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in treatment of anal fissure

Lancet. 1997 Jan 4;349(9044):11-4. doi: 10.1016/S0140-6736(96)06090-4.


Background: Anal fissure is most commonly treated surgically by internal anal sphincterotomy. However, there is some concern over the effects of this procedure on continence. Nitric oxide donors such as glyceryl trinitrate (GTN) have been shown to cause a reversible chemical sphincterotomy capable of healing fissures in a small series of cases. This study reports a prospective, randomised, double-blind, placebo-controlled trial to test the hypothesis that topical GTN is the best first-line treatment for chronic anal fissure.

Methods: 80 consecutive patients were randomised to receive treatments with topical 0.2% GTN ointment or placebo. Maximum anal resting pressure (MARP) was measured with a constantly perfused side-hole catheter before and after the first application of trial ointment. Anodermal blood flow was measured during manometry by laser Doppler flowmetry. After initial treatments, patients were given a supply of ointment (either GTN or placebo) to be applied to the lower anal canal twice daily. Patients were reviewed 2-weekly. At the initial and follow up visits patients were asked to record pain experienced on defaecation on a linear analogue pain score. Endpoints were healing of the fissure or condition after 8 weeks of treatment.

Findings: After 8 weeks, healing was observed in 26/38 (68%) patients treated with GTN and in 3/39 (8%) patients treated with placebo (p < 0.0001, chi 2 test). Linear analogue pain score fell significantly in both groups after 2 weeks of treatment. This fall was maintained in those treated with GTN but pain scores returned to pre-treatment values by 4 weeks on treatment with placebo. MARP fell significantly from a mean of 115.9 (SD 31.6) to 75.9 (30.1) cm H2O (p < 0.001, Student's paired t-test) in patients treated with GTN but no change was seen in MARP after placebo. Anodermal blood flow measured by laser Doppler flowmetry significantly increased after application of GTN ointment but was unaffected by placebo.

Interpretation: Topical GTN provides rapid, sustained relief of pain in patients with anal fissure. Over two-thirds of patients treated in this way avoided surgery which would otherwise have been required for healing. Long-term follow up is needed to assess the risk of recurrent fissure in patients with GTN.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Chronic Disease
  • Double-Blind Method
  • Fissure in Ano / drug therapy*
  • Humans
  • Nitroglycerin / therapeutic use*
  • Ointments
  • Pain Measurement
  • Placebos
  • Prospective Studies
  • Treatment Outcome


  • Ointments
  • Placebos
  • Nitroglycerin