Barak Nir, Gecse Krisztina B, Takács István
RDD Pharma ltd, Tel-Aviv, Israel.
Semmelweis University, 1st Department of Internal Medicine, Budapest, Hungary.
Dis Colon Rectum. 2019 Feb;62(2):234-240. doi: 10.1097/DCR.0000000000001265.
Topical α-agonists contract the internal anal sphincter muscle; therefore, they may serve as treatment for fecal incontinence.
The aim of this study was to investigate the effect of the α-agonist oxymetazoline 1.0% on fecal incontinence in patients with spinal cord injury.
This was a double-blind, crossover study. Before randomization, all patients underwent a 1-day, open-label anal manometry and pharmacokinetic study.
The study was conducted at the Department of Internal Medicine, Semmelweis University, Hungary.
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.
The primary outcome measured was the number of fecal incontinence episodes in the 8 and 12 hours after drug administration.
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.
The study was limited by the small number of participants.
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.
局部用α-激动剂可使肛门内括约肌收缩；因此，它们可用于治疗大便失禁。
本研究旨在调查1.0%的α-激动剂羟甲唑啉对脊髓损伤患者大便失禁的影响。
这是一项双盲交叉研究。在随机分组前，所有患者均接受为期1天的开放标签肛门测压和药代动力学研究。
该研究在匈牙利塞梅尔维斯大学内科进行。
19名患者被纳入一项随机双盲、安慰剂对照的临床试验，该试验有两个组：安慰剂组4周，随后羟甲唑啉组4周，或反之，在交叉试验设计中有2周的洗脱期。治疗顺序随机分配，通过每日日记记录大便失禁情况。
测量的主要结局是给药后8小时和12小时内大便失禁发作的次数。
使用羟甲唑啉后静息肛门压力升高（25.2%）。每月平均大便失禁发作次数（用药后12小时）的变化显示，羟甲唑啉优于安慰剂：26.3（标准差±28.4）对36（标准差±39.8）（p = 0.021）。仅纳入非气体发作时，每月大便失禁发作的平均次数从10.1（+4.3）降至6.3（±2.1）次（p = 0.022）。治疗期和安慰剂期之间在不良事件方面未观察到差异。所有药代动力学样本均低于检测限。
该研究受参与者数量较少的限制。
在本研究中，羟甲唑啉凝胶呈现出明显的临床有益效果，且安全性和耐受性良好。药代动力学分析结果表明，临床益处主要归因于羟甲唑啉的局部作用。计划开展未来研究以调查更高剂量的羟甲唑啉用于该适应症的情况。见视频摘要：http://links.lww.com/DCR/A797 。
