Randomized clinical trial Blinded randomized clinical trial of botulinum toxin versus isosorbide dinitrate ointment for treatment of anal fissure S. Festen, S. S. Gisbertz, F. van Schaagen and M. F. Gerhards Department of Surgery, Onze Lieve Vrouwe Gasthuis, Oosterpark 9, 1091 AC Amsterdam, The Netherlands Correspondence to: Mr S. Festen (e-mail: Sebastiaanfesten@yahoo.com) Background: Nitric oxide donors such as isosorbide dinitrate (ISDN) are considered the first choice of treatment for anal fissure. After reports of the successful treatment of such fissures with botulinum toxin, this randomized blinded trial compared botulinum toxin with ISDN in the treatment of chronic anal fissure. Methods: Patients were randomized to receive an injection of botulinum in the internal anal sphincter and a placebo ointment, or a placebo injection and ISDN ointment. The primary endpoint was macroscopic fissure healing after 4 months. Results: After 4 months macroscopic healing of the fissures was noted in 14 of 37 patients in the botulinum group and 21 of 36 in the ISDN group. Pain scores were lower among patients who received ISDN, although the difference was not significant. Side-effects were similar in the two groups. Conclusion: In contrast with previous reports on botulinum toxin as a therapeutic agent for anal fissure, this study found no advantage over treatment with a nitric oxide donor as regards fissure healing and fissure-related pain. Paper accepted 10 June 2009 Published online in Wiley InterScience (www.bjs.co.uk). DOI: 10.1002/bjs.6747 Introduction An anal fissure is an ulcer or split located in the squamous epithelium of the anus. It predominantly occurs in the posterior midline 1,2 . The aetiology is debated, but spasm of the internal anal sphincter (IAS) is likely to play an essential role in the pathophysiology 3,4 . Pain, during and after defaecation, is the main symptom and can be disabling. Anal bleeding may occur intermittently. Successful treatment results in an improved quality of life 5 . The mainstay of current therapy is directed at lowering the resting pressure of the IAS. Historically this was achieved surgically, but therapy has shifted towards pharmacological treatment owing to the high incidence of incontinence-related complications 6 . Topical isosorbide dinitrate (ISDN) has long been the pharmacological treatment of choice in the Netherlands. It acts as a nitric oxide donor, lowering IAS pressure and producing vasodilatation in the anoderm 7 . Another commonly used nitric oxide donor is glyceryl trinitrate (GTN) 8–10 . In a recent review of both nitrate oxide donors, the mean healing rate was approximately 65 per cent 6 . Treatment of anal fissures with botulinum toxin was first described in 1993 by Jost and Schimrigk 11 . Injec- tion of botulinum toxin into the anal sphincter blocks acetylcholine release, thereby stopping neural transmis- sion, causing transient hypotonia of the sphincter 12 . Since the randomized controlled trial of botulinum toxin ver- sus topical nitroglycerine 13 , botulinum toxin has become increasingly popular and has been compared with other treatment modalities 6 . This double-blind randomized trial compared botulinum toxin with ISDN in the treatment of chronic anal fissure. Methods All consecutive patients over the age of 18 years presenting to a surgical outpatient clinic with a chronic anal fis- sure between June 2002 and March 2006 were eligible for inclusion in the study. The fissure was considered chronic if symptoms had been present for at least 4 weeks, and phys- ical examination showed typical signs such as visible fibres of the IAS and a sentinel pile. Exclusion criteria were preg- nancy, previous anal surgery, Crohn’s disease and systemic Copyright  2009 British Journal of Surgery Society Ltd British Journal of Surgery 2009; 96: 1393–1399 Published by John Wiley & Sons Ltd