Topical Oxymetazoline for Fecal Incontinence in Patients with Spinal Cord Injury: A Double-Blind Randomized Controlled Crossover Study

Abstract

BACKGROUND: Topical &agr;-agonists contract the internal anal sphincter muscle; therefore, they may serve as treatment for fecal incontinence. OBJECTIVES: The aim of this study was to investigate the effect of the &agr;-agonist oxymetazoline 1.0% on fecal incontinence in patients with spinal cord injury. DESIGN: This was a double-blind, crossover study. Before randomization, all patients underwent a 1-day, open-label anal manometry and pharmacokinetic study. SETTINGS: The study was conducted at the Department of Internal Medicine, Semmelweis University, Hungary. PATIENTS: Nineteen patients were enrolled into a randomized double-blind, placebo-controlled clinical trial with 2 arms: placebo for 4 weeks followed by oxymetazoline for 4 weeks, or vice versa, with an interval 2-week washout period, in a crossover trial design. Treatment order was randomly assigned, and fecal incontinence was captured with daily diaries. MAIN OUTCOME MEASURES: The primary outcome measured was the number of fecal incontinence episodes in the 8 and 12 hours after drug administration. RESULTS: Resting anal pressure increased in response to oxymetzoline (25.2%). The change in the mean fecal incontinence episodes per month (12 hours post drug application) favored oxymetazoline over placebo: 26.3 (SD ±28.4) versus 36 (SD ±39.8) (p = 0.021). When only nongas episodes were included, the mean number of episodes decreased from 10.1 (+4.3) to 6.3 (±2.1) fecal incontinence episodes per month (p = 0.022). No difference was observed in adverse events between treatment and placebo periods. All pharmacokinetic samples were below the detection limit. LIMITATIONS: The study was limited by the small number of participants. CONCLUSIONS: In this study, oxymetazoline gel presented a clear clinical beneficial effect accompanied by a favorable safety and tolerability profile. Results of the pharmacokinetic analysis indicate that the clinical benefit was mainly due to a local effect of oxymetazoline. Future studies are planned to investigate higher doses of oxymetazoline for this indication. See Video Abstract at http://links.lww.com/DCR/A797.