Title: A randomised comparison of the Fenix® magnetic anal sphincter versus sacral nerve stimulation for adult faecal incontinence.
Funder: Department of Health and Social Care

Abstract: Design: A prospective, UK multi-centre, parallel-group, randomised controlled trial investigating the safety and efficacy of the Fenix® magnetic anal sphincter (MAS) for adult faecal incontinence (FI). The comparator is sacral nerve stimulation (SNS), a NICE recommended treatment for FI resistant to conservative therapies. Setting: NHS Coloproctology Units in secondary care, with membership of ACPGB&I and experience in SNS. Target population: Adult patients (18 years or older) with FI symptoms for more than 6 months, suffering 2 or more incontinent episodes per week, and suitable and willing to undergo either SNS or Fenix® MAS implantation. Excluded patients include those with gastrointestinal motility disorders, obstructed defaecation, external rectal prolapse, anal sphincter defect >180°,an electric or metallic implant within 10cm of anal canal, anorectal sepsis, diagnosis of colorectal or anal cancer within 2 years, significant scarring of the anorectum, pregnancy, immunocompromised, congenital spinal abnormalities, and requirement for future MRI surveillance. Health technologies being assessed: The Fenix® Continence Restoration System (Torax Medical Inc., Minnesota, USA) is a new device for FI resistant to medical therapies. It consists of a ring of titanium beads with magnetic cores, placed surgically to reinforce the anal sphincter. To defecate, the patient simply pushes as in normal defecation and the force generated separates the beads to allow the stool through the anal canal. Continence is restored by passive attraction of the magnetic beads. Once implanted, the device does not require patient input in order to function. The book price for Fenix® MAS is £4,000. Data on efficacy is limited, but suggests a 50-percent improvement in continence in 70% of patients. Complications can occur in ~20% of patients, leading to explantation in ~10%. Fenix™ MAS will be compared with SNS, a NICE recommended treatment for FI resistant to conservative therapies. In the UK, between 2006 and 2009, 1395 permanent SNS devices were implanted with figures for 2011 approaching 600 devices (Medtronic UK). SNS works by a combination of anal sphincter augmentation and modulation of spinal/supra-spinal pathways. A temporary stimulation period is undertaken and judged a success if a greater than 50% reduction of incontinent symptoms is achieved. Around 70% of patients have a good response and proceed to a permanent implant. Of these, 10% never gain any significant improvement and 26% experience loss of efficacy, usually within the first year. There is an explant rate of ~2% due to complications. Thus, from a decision-to-treat, the long-term efficacy is around 45% - 50%. SNS is also expensive; components cost for both temporary and permanent implants are ~£9,588, excluding hospital costs, on-going re-programming costs, and battery replacement every 6-7 years (~£7,400). Measurements of costs and outcomes: Data will be collected at baseline, surgery, 2-weeks postoperative, and at 6-, 12-, and 18-months post-randomisation. Disease-specific, validated, scoring systems will include: i) Cleveland Clinic Incontinence Score (CCIS) to determine the frequency and severity of incontinent episodes, ii) Obstructed Defaecation Score (OD-score) to determine constipation symptoms, iii) Faecal Incontinence Quality of Life (FIQoL) score to assess the impact of faecal incontinence on quality of life, and iv) the generic SF-12 QoL score. Health economics data will be derived from the EQ-5D tool supplemented with HES data and health and social resource use questionnaires. Sample size: 350 patients will be required to detect at least a 20% difference in the percentage of successes at 18 months post randomisation (where success is defined to be: device in situ and =50% CCIS improvement from baseline) between MAS and SNS at 5% level of significance, 90% power, assuming approximately 40% success on the SNS arm and allowing for 20% loss to follow-up. A sample size of 350 patients is also expected to sufficiently guard against the potential adverse effects of clustering by surgeon on the study power. Assuming that the number of patients recruited per surgeon is no larger than 15 (i.e. recruitment of at least 24 surgeons to the trial), a sample size of 350 patients will yield at least 80% power for intra-cluster correlation coefficients (ICCs) as large as 0.025. Project timetable including recruitment: 32 centres have been identified that provide SNS for adult faecal incontinence. All centres are NHS Coloproctology Units with membership of ACPGB&I. In 2011, these 32 centres implanted a total of 575 permanent SNS implants (Medtronic UK). It is estimated that at least 20 of the 32 centres will participate with a conservative recruitment of 7 patients per centre per year, allowing 350 patients to be recruited over a period of 30 months. 12 months is required to set-up the study and initiate site contact, hold 4 surgeon-training workshops, and complete the learning curve of 3 MAS implants; the 20 planned sites will start recruitment in months 12-24. Recruitment will run for 2.5 years (months 13 to 42). Follow-up will be for 18 months from the time of randomisation (months 43 to 60), with a 6-month post-study period for data analysis and write-up. The total duration of the study will be 66 months. Expertise in the team: The study will be run under the auspices of the ACPGB&I (DGJ, Chair of R&A Committee). It will be sponsored by the University of Leeds (UoL) and conducted by the Clinical Trials Research Unit (CTRU), Leeds. DGJ will provide surgical expertise and leadership skills. He will be supported by GT, NIHR Clinical Lecturer, SB (Colorectal Surgeon, Sheffield), and KN (Senior Lecturer, Southampton, and President-elect to ACPGB&I). JB is Director of CTRU and brings expertise in medical statistics and running large clinical trials. She will be supported by VN, Operations Director, and FC, Clinical Director of CTRU. Health economics is represented by CH, Professor of Economics at UoL. DP, consultant liaison psychiatrist, will provide expertise in the psychological aspects of FI, and JL, Senior Community Incontinence Advisor to Leeds PCT, will bring the primary care perspective. PPI will include local input from Leeds PPIR along with representation from sufferers of faecal incontinence and the support and means of the Bladder and Bowel Foundation.

Lay abstract: Faecal incontinence (FI) is a distressing condition that affects between 5% and 10% of the adult population. It is more common with advancing age, and is a particularly common problem in residential and nursing care homes; it is the second most common cause of admission to a nursing home. It impacts on social, physical, and mental well-being and is a substantial burden on NHS health resources. Current treatment options for moderate to severe FI are limited in their long-term efficacy. Sacral nerve stimulation (SNS) is recognised by the National Institute for Health and Clinical Excellence (NICE) as an effective treatment for FI that is resistant to simple measures. It involves the placement of a fine electrode through the skin and onto a nerve that supplies the lower bowel. It is performed as a two-stage procedure: a temporary stimulation phase to determine whether the device improves incontinence, and if this is the case, then a permanent SNS device is implanted. Some 70% of patients proceed from temporary stimulation to a permanent implant. In 26% of patients who have a permanent implant there is a loss of benefit. A further 2-5% suffer irresolvable complications. Overall, only 50% of patients thought to be eligible for SNS have a functioning device in the long-term. SNS is also expensive with the device alone costing ~£10,000 and the need for regular re-programming and battery replacement requiring further surgery. More recently, a novel magnetic anal sphincter (Fenix® MAS, Torax Medical Inc, Minnesota, USA) has been introduced for the treatment of FI. It consists of a ring of titanium beads with magnetic cores, placed surgically to reinforce the anal sphincter. To defecate, the patient simply pushes as in normal defecation and the force generated separates the beads to allow the stool through the anal canal. Continence is restored by passive attraction of the magnetic beads. Once implanted, the device does not require patient input in order to function. The Fenix® MAS costs £4,000. Preliminary results are promising with some 70% of patients reporting a benefit. But, studies have been small and a more rigorous evaluation is required prior to its widespread adoption. In order to properly evaluate the role of Fenix® MAS in the treatment of FI, we will compare it to SNS, which is a NICE recommended treatment for FI. The study will take place in dedicated Coloproctology Units throughout the UK that have experience with the SNS technique. Adult patients suffering with FI will be approached for inclusion in the study if they have significant incontinence symptoms and are suitable and willing to undergo surgery. A number of patients with FI will not be suitable for the study because they have other conditions that preclude placement of an implantable device. Patients who give consent to take part in the study will be randomly allocated to receive either the Fenix® MAS or SNS device. All patients will be monitored closely during the study to determine the benefits of the treatment received and any complications. These will be recorded on scoring sheets and questionnaires specially designed to capture FI symptoms, constipation symptoms, quality of life, and the costs involved with each treatment. In total, 350 patients will be included in the study to be sure that we can reliably tell a difference between the two treatments (Fenix® MAS and SNS) in terms of improvement in continence symptoms. The study will be undertaken in conjunction with the Association of Coloproctology of GB&I (ACPGB&I), which is the main UK professional association for surgeons undertaking surgery for bowel conditions. The study will be coordinated by the Clinical Trials Research Unit at the University of Leeds, who are experienced in running large clinical trials in colorectal surgery. The study will also be supported by the Bladder & Bowel Foundation (B&BF), a UK wide charity that provides information and advice on a range of symptoms and conditions related to the bladder and bowel. The B&BF will provide patient and clinical views and comments, as well as supporting the promotion and dissemination of information and outcomes resulting from the project.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: ORAL AND GASTROINTESTINAL