Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure

Br J Surg. 2002 Apr;89(4):413-7. doi: 10.1046/j.0007-1323.2001.02042.x.

Abstract

Introduction: Glyceryl trinitrate (GTN) ointment (0 small middle dot2 per cent) has an efficacy of up to 68 per cent in healing chronic anal fissure, but with headache as a major side-effect. Diltiazem hydrochloride (DTZ) cream (2 per cent) is expected to have fewer side-effects.

Methods: A prospective double-blind randomized two-centre trial requiring at least 26 patients in each group (alpha = 0.05, beta = 0.9) was instituted after approval of the local ethics committee, to compare the incidence of side-effects (primary endpoint) with 0.2 per cent GTN ointment and 2 per cent DTZ cream in the treatment of chronic anal fissure. Treatments were applied perianally, twice daily for 6-8 weeks. All patients gave written informed consent.

Results: Both groups were comparable in patient demographics and clinical characteristics. Twelve patients violated the protocol, withdrew or did not attend follow-up. There were more side-effects with GTN (21 of 29 patients) than with DTZ (13 of 31) (relative risk (RR) 1.84 (95 per cent confidence interval (c.i.) 1.11 to 3.04), P = 0.01). In particular, more headaches occurred with GTN (17 of 29 patients) than with DTZ (eight of 31) (RR 2.06 (95 per cent c.i. 1.18 to 3.59), P = 0.01). There were no significant differences in healing and symptomatic improvement rates between patients receiving GTN (25 of 29) and DTZ (24 of 31).

Discussion: DTZ cream caused substantially fewer headaches than GTN ointment. There was no significant difference in the healing or improvement of chronic anal fissure between the treatments. DTZ may be the preferred first-line treatment for chronic anal fissure.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Diltiazem / administration & dosage
  • Diltiazem / adverse effects*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fissure in Ano / drug therapy*
  • Follow-Up Studies
  • Headache / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Nitroglycerin / administration & dosage
  • Nitroglycerin / adverse effects*
  • Ointments
  • Pain Measurement
  • Prospective Studies
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / adverse effects*

Substances

  • Ointments
  • Vasodilator Agents
  • Diltiazem
  • Nitroglycerin