Randomised controlled trial compairing locally made glycerine trinitrate cream treatment to manual dilatation of anus in acute anal fissure at the University Teaching Hospital

Abstract

There are various ways of treating acute fissure in ano, broadly categorized as conservative and surgical methods. At The University Teaching Hospital (UTH) Lusaka Zambia, acute fissure in ano is mainly treated by maual dilatation of the anus (MDA) while various studies elsewhere in other countries have shown that application of topical glycerine trinitrate (GTN) is potent and cost effective in the treatment of this condition. However GTN cream is not commercially available in Zambia. Therefore, in this study, we compared treatment of acute anal fissure by MDA to treatment with locally made topical 0.25% GTN cream. The objective of the study was to assess the potency and cost effectiveness of locally made 0.25% GTN cream and compare with the existing MDA method in the treatment of acute fissure in ano. We enrolled 68 patients in a randomized controlled trial which was conducted in a period of 8 months from August 2011 to April 2012 at UTH Lusaka, Zambia. The minimum age for enrolment was 18 years and only patient with acute ano pain duration of up to 6 weeks and without history of previous treatment for a similar condition or with another anal condition were considered for entry. Two cohorts were created; MDA (control) and GTN (intervention), each with 34 participants. Allocation was done by using a randomized computer number generator using groups of four, then labeled papers placed in opaque envelops. Participants picked an envelope from the top of the pack for their allocation to either MDA or GTN cohort depending on its content. 0.25% GTN was prepared by UTH pharmacy by dissolving 210 GTN tablets each weighing 500 micrograms in 20ml of KY Jelly. The participants in the MDA cohort were treated by manually dilating the anus under general anesthesia whereas those in the GTN cohort were treated with topical 0.25% glycerine trinitrate cream which was applied to the fissure twice daily by themselves. Participants were followed up for 6 weeks after initiation of treatment. They were reviewed at 2, 4 and 6 weeks intervals during which fissure healing was assessed. The primary outcome was fissure healing defined as total absence of pain at 6 weeks. ix All the participants reached the end point of the study. Healing for the MDA at 6 weeks was 28 (82.4%) while for the 0.25% GTN group was 31(91.2%) giving a relative risk (RR) of 1.11 (0.91-1.33) at 95% confidence level. Hence there was no significant difference in the outcome of the two methods at the end of the treatment period. However, prior to 6 weeks a significant difference in the treatment methods was observed (RR=0.22 (0.05-0.95) at 2 weeks, RR=0.41 (0.22-0.75) at 4 weeks). Respondency to treatment was observed to be better in the MDA before 6 weeks. 89% of the participants were observed to have fissure posteriorly or at six o’clock position. Cost of treatment with MDA compared with locally made GTN cream was observed to be three (3) times more. The HIV rate was 13.2% among those who took the test and had no influence in the treatment outcome for both cohorts. Other than mild headache in 6 participants in the GTN cohort, no other adverse effects were observed. In conclusion, outcome of treatment of acute fissure in ano with locally made topical 0.25% GTN cream compared with MDA is the same at 6 weeks. Both methods are equally effective in the treatment of fissure in ano. However in terms of respondency to treatment, MDA shows a better result in the first four (4) weeks of treatment. Therefore effectiveness of locally made GTN cream comes at an expense of delayed despondency to treatment. GTN cream is safe and potent, hence it should be adopted for use in acute fissure in ano treatment as second line treatment to MDA at The University Teaching Hospital and first line treatment in periphery hospitals where theatres services are not available and where general anesthesia or spinal anaesthesia cannot be administered.