Purpose
This study was designed to assess the safety and efficacy of 0.2 percent glyceryl trinitrate suppository form in the healing of chronic anal fissure.
Methods
Thirty-four patients with symptomatic chronic anal fissures were assigned to 0.2 percent glyceryl trinitrate suppository (n = 21) or placebo (n = 13) in a double blind design. Patient's symptom scores were registered at first visit. A validated daily chart was given to assess their symptoms on a daily basis. Both groups received psyllium from the beginning of the study. They were assessed at two-week intervals for six weeks. Then, they started a washout period of one month and after that were crossed over for another six weeks. Chi-squared, t-tests, and analysis of variance were used for statistical analysis.
Results
Complete healing at six weeks was achieved in 12 of 21 patients (57 percent) in the glyceryl trinitrate group and 5 of 13 patients (38 percent) in the placebo (P < 0.05).The overall healing rates at the end of study were 15 of 21 (71 percent) vs. 11 of 13 (84 percent) in the glyceryl trinitrate and placebo groups, respectively (P > 0.05).
Conclusions
Application of 0.2 percent glyceryl trinitrate suppository form represents a new, promising, and effective treatment for chronic anal fissure.
Similar content being viewed by others
References
Khan H, Shukr I, Munir SH, et al. Effect of topical glyceryl trinitrate on the management of acute anal fissure. Rawal Med J J Pakistan Med Assoc 2006;31:1–4.
Pescatori M, Interisano A. Annual report of the Italian coloproctology units. Tech Coloproctol 1995;3:29–30.
Jonas M, Scholefield JH. Anal fissure. Gastroenterol Clin North Am 2001;30:167–81.
Sailer M, Bussen D, Debus ES, Fuchs KH, Thiede A. Quality of life in patients with benign anorectal disorders. Br J Surg 1998;85:1716–9.
McCallion K, Gardiner KR. Progress in the understanding and treatment of chronic anal fissure. Postgrad Med J 2001;77:753–8.
Minguez M, Tomas-Ridocci M, Garcia A, et al. Pressure of the anal canal in patients with haemorrhoids or with anal fissure. Effect of the topical application of an anaesthetic gel. Rev Esp Enferm Dig 1992;81:103–7.
Notaras MJ. Lateral subcutaneous sphincterotomy for anal fissure—a new technique. Proc R Soc Med 1969;62:713.
Khubchandani IT, Reed JF. Sequelae of internal sphincterotomy for chronic fissure in ano. Br J Surg 1989;76:431–4.
Christie A, Guest JF. Modelling the economic impact of managing a chronic anal fissure with a proprietary formulation of nitroglycerin (Rectogesic) compared to lateral internal sphincterotomy in the United Kingdom. Int J Colorectal Dis 2002;17:259–67.
Svendsen CB, Matzen P. Treatment of chronic anal fissure with topically applied nitroglycerin ointment. A systematic review of evidence-based results. Ugeskr Laeger 2002;164:3845–9.
Scholefield JH, Bock JU, Marla B, et al. A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in patients with chronic anal fissures. Gut 2003;52:264–9.
Liberting G, Knight JS, Farouk R. Randomised trial of topical 0.2% glyceryl trinitrate and lateral internal sphincterotomy for the treatment of patients with chronic anal fissure: long-term follow-up. Eur J Surg 2002;168:418–21.
Jonas M, Lund JN, Scholefield JH. Topical 0.2% glyceryl trinitrate ointment for anal fissures: long-term efficacy in routine clinical practice. Colorectal Dis 2002;4:317–20.
Tankova L, Yoncheva K, Muhtarov M, Kadyan H, Draganov V. Topical mononitrate treatment in patients with anal fissure. Aliment Pharmacol Ther 2002;16:101–3.
Sonmez K, Demirogullari B, Ekingen G, et al. Randomized, placebo-controlled treatment of anal fissure by lidocaine, EMLA, and GTN in children. J Pediatr Surg 2002;37:1313–6.
Simpson J, Lund JN, Thompson RJ, Kapila L, Scholefield JH. The use of glyceryl trinitrate (GTN) in the treatment of chronic anal fissure in children. Med Sci Monit 2003;9:PI123–6.
Ward DI, Miller BJ, Schache DJ, et al. Cut or paste? The use of glyceryl trinitrate paste in the treatment of acute and chronic anal fissure. ANZ J Surg 2000;70:19–21.
Skinner SA, Polglase AL, Le CT, Winnett JD. Treatment of anal fissure with glyceryl trinitrate in patients referred for surgical management. ANZ J Surg 2001;71:218–20.
Ehrenpreis ED, Rubin DT, Ginsburg PM, Meyers JS. Treatment of anal fissures with topical nitroglycerin. Expert Opin Pharmacother 2001;2:41–5.
Rattan S, Sarkar A, Chakder S. Nitric oxide pathway in rectoanal inhibitory reflex of opossum internal anal sphincter. Gastroenterology 1992;103:43–50.
O’Kelly T, Brading A, Mortensen N. Nerve mediated relaxation of the human internal anal sphincter: the role of nitric oxide. Gut 1993;34:689–93.
Stebbing JF. Nitric oxide synthase neurones and neuromuscular behaviour of the anorectum. Ann R Coll Surg Engl 1998;80:137–45.
Loder PB, Kamm MA, Nicholls RJ, et al. “Reversible chemical sphincterotomy” by local application of glyceryl trinitrate. Br J Surg 1994;81:1386–9.
Guillemot F, Leroi H, Lone YC, et al. Action of in situ nitroglycerin on upper anal canal pressure of patients with terminal constipation. A pilot study. Dis Colon Rectum 1993;36:372–6.
Carapeti EA, Kamm MA, McDonald PJ, et al. Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not more effective, and there is a high recurrence rate. Gut 1999;44:727–30.
Dorfman G, Levitt M, Platell C. Treatment of chronic anal fissure with topical glyceryl trinitrate. Dis Colon Rectum 1999;42:1007–10.
Cundall JD, Gunn J, Easterbrook JR, Tilsed JV, Duthie GS. The dose response of the internal anal sphincter to topical application of glyceryl trinitrate ointment. Colorectal Dis 2001;3:259–62.
Graziano A, Svidler Lopez L, Lencinas S, et al. Long-term results of topical nitroglycerin in the treatment of chronic anal fissures are disappointing. Tech Coloproctol 2001;5:143–7.
Jonas M, Lobo DN, Gudgeon AM. Lateral internal sphincterotomy is not redundant in the era of glyceryl trinitrate therapy for chronic anal fissure. J R Soc Med 1999;92:186–8.
Aslani A, Tavakoli N, Emami MH, Asadi F. Preparation and evaluation of physicochemical properties of glyceryl trinitrate suppository in the treatment of anal fissure. In: The 4th International Postgraduate Research Symposium on Pharmaceutics, Istanbul, Turkey, September 20 to 22, 2004.
O’Kelly T, Brading A, Mortensen N. Nerve mediated relaxation of the human internal anal sphincter: the role of nitric oxide. Gut 1993;34:689–93.
Rattan S, Chakder S. Role of nitric oxide as a mediator of internal anal sphincter relaxation. Am J Physiol 1992;262:G107–12.
Lund JN, Scholefield JH. Glyceryl trinitrate is an effective treatment for anal fissure. Dis Colon Rectum 1997;40:468–70.
Acknowledgments
The authors thank friends at Poursina Hakim Research Institute, Isfahan Medical Student Research Committee, and Miss Aliyari for their kind support.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by Isfahan University of Medical Sciences and Poursina Hakim Research Institute.
Read at the Iranian Congress of Gastroenterology and Hepatology (ICGH 2006), Tehran, Iran.
About this article
Cite this article
Emami, M.H., Sayedyahossein, S. & Aslani, A. Safety and Efficacy of New Glyceryl Trinitrate Suppository Formula: First Double Blind Placebo-Controlled Clinical Trial. Dis Colon Rectum 51, 1079–1083 (2008). https://doi.org/10.1007/s10350-008-9226-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10350-008-9226-3