Randomised Mixed Methods Pilot Trial of Sacral and Percutaneous Tibial Nerve Stimulation for Faecal Incontinence

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1 Research for Patient Benefit Randomised Mixed Methods Pilot Trial of Sacral and Percutaneous Tibial Nerve Stimulation for Faecal Incontinence Thin NN 1, Taylor SJC 2, Bremner SA 2, Hounsome N 2, Alam A 3, Emmanuel AV 3, Bannister S 1, Williams NS 1, Allison ME 1, Vaizey CJ 4, Thomas GP 4, Knowles CH 1 1. National Centre of Bowel and Surgical Innovation, Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University London & Barts Health NHS Trust. 2. Pragmatic Clinical Trials Unit, Centre for Primary Care and Public Health, Barts and the London School of Medicine & Dentistry, Queen Mary University London. 3. GI Physiology Unit, University College Hospital, London 4. The Sir Alan Parks Department of Physiology, St Mark's Hospital and Academic Institute, London.

2 Introduction Faecal incontinence (FI) is common and debilitating Sacral Nerve Stimulation (SNS) is an established surgical treatment Percutaneous Tibial Nerve Stimulation (PTNS) is newer NICE guidance and NHS Commissioning position in UK for PTNS is uncertain Effectiveness, cost and acceptability of these treatments have not been systematically compared

3 Interventions Sacral nerve stimulation InterStim TM Medtronic PNE phase 3065 unipolar lead under LA 3625 external pulse generator 14 days Percutaneous tibial nerve stimulation Uroplasty Urgent PC success Permanent stimulator under LA or GA quadripolar tined lead 3058 implantable pulse generator 12 initial weekly sessions 30 minutes per session 3 top up sessions over 2 months Equipment cost 10, ITT outcomes 5565% % 2 Operations usually Thin et al., BJS Horrocks et al., BJS 2014

4 Aims Pilot mixed methods trial of SNS vs. PTNS to determine: 1. Estimates of effect size for main clinical outcomes 2. Health economics 3. Qualitative data on patient experience

5 Design overview Parallel arm N = 40 patients with FI 3 site recruitment (BH, UCLH and StM) Randomised allocation performed remotely minimised by sex and symptom severity ratio predetermined 23: 17 Observerblinded (quantitative outcomes) Qualitative study

6 Patients 6

7 Results

8 Results: baseline cohorts Stratified by gender and FI severity Random allocation 23 SNS:17 PTNS Demographic PTNS Total N BLT UCH 2 3 Female 17 (100%) 22 (96%) Age 59 years (sd 11.1) 59 years (sd 13.2) SNS History Postpartum aetiology 10 (59%) 10 (45%) Traumatic deliveries 0.6 (sd 0.5) 0.7 (sd 1.0) Hysterectomy 7 (41%) 12 (55%) Previous / ongoing treatments Previous anal Sphincter repair 0 (0%) 2 (9%) Nurse led conservative management 12 (71%) 17 (74%) Biofeedback 4 (24%) 11 (48%) Incontinence pad usage 9 (53%) 23 (100%) Anal plug 0 (0%) 1 (4%) Antidiarrhoeal medications 8 (47%) 17 (74%) Suppository use 2 (12%) 7 (30%) Enema use 1 (9%) 1 (4%) Irrigation 2 (12%) 2 (9%) Main Symptoms Severity < 6 FI episodes/week 12 (71 %) 16 (70%) Severity >6 FI episodes /week 5 (29%) 7 (30%) Urge Incontinence 14 (82%) 21 (91%) Passive Incontinence 15 (88%) 20 (87%) Flatus Incontinence 16 (94%) 20 (87%) Unable to defer defaecation 13 (76%) 20 (87%) Soiling 16 (94%) 21 (91%) Evacuatory difficulties 11 (65%) 10 (43%)

9 Consort diagram Eligible N=91 9 Recruited and Randomised N=40 SNS N=23 PTNS N=17 Withdrawn before intervention N=4 Withdrawn before intervention N=1 Trial of Temp SNS N=19 Completed PTNS N=16 Passed Temp SNS N=16 Failed Temp SNS N=3 Complete data collection N=16 Withdrawn from treatment N=1 Complete data collection N=2 Withdrawn from interview N=1 Perm SNS and complete data collection N=15 ethics: REC 10/H0808/38

10 (a) 10 (c) (b) Main outcomes of percutaneous tibial nerve stimulation (PTNS) and sacral nerve stimulation (SNS) at 3 and 6 months compared to baseline: (a) prevalence of faecal incontinence episodes per week; (b) Cleveland clinic incontinence scores. Bars represent mean + standard deviation; (c) bar frequency chart showing quartiles of percentage change in FI episodes per week from baseline.

11 11 Clinical outcomes Intervention PTNS (n=17) SNS ITT (n=23) SNS PP (permanent implant) (n=15) Visit Baseline 3 months 6 months Baseline 3 months 6 months Baseline 3 months 6 months N Effect sizes Diff. total FI episodes per week 4.8 (9.5 to 0) 4.3 (10.5 to 1.9) 7.9 (13.6 to 2.2) 6.6 (12.4 to 0.7) 9.3 (16.2 to 2.3) 9 (15.2 to 2.8) Diff. CCI score 3.6 (5.4 to 1.9) 3.2 (4.8 to 1.5) 5.1 (7.6 to 2.5) 6 (8.7 to 3.3) 6.3 (9.2 to 3.3) 7.2 (10.3 to 4.1) 50% reduction in FIE per week 38% (50%) 44% (51%) 47% (51%) 61% * (50%) 53% (52%) 67% (49%) Quality of life instruments Diff. EQ5D 0.1 (0.1 to 0.2) 0.1 (0.1 to 0.2) 0.0 (0.1 to 0.1) 0.1 (0 to 0.2) 0.0 (0.2 to 0.2) 0.1 (0.0 to 0.2) Diff. FIQL (aggregate) 1.7 ( ) 1.0 ( ) 2.9 ( ) 2.9 ( ) 3.7 ( ) 3.7 ( ) Summary c.f. 71% Horrocks et al., BJS 2014 * c.f. 63% Thin et al., BJS 2013

12 Health economics In trial Health care resources with 6 months FU (ITT) SNS: 12,748 (sd: 4,175) PTNS: 2,356 (sd: 122) Health outcome: QALY SNS: (sd: 0.102) PTNS: (sd: 0.170) ACER (average costeffectiveness ratio) (calculated as cost/qaly) SNS: 37,166 PTNS: 7,880

13 Qualitative assessment Both treatments highly acceptable Patients experience: SNS slightly greater benefit vs. PTNS Positive super ordinate themes Improved self confidence Improved hygiene Optimism for future Negative super ordinate themes Long distances and time to travel to therapy; Anxiety re: surgery (SNS only)

14 Limitations Pilot design Small number patients Shortterm follow up (6 months) Study withdrawals (preference)

15 Conclusions SNS and PTNS both supported by observational (clinical) data SNS vs. PTNS o o o SNS appears slightly better but more expensive at shortterm time horizon Both treatments safe and highly acceptable Some effects of preference Definitive trial very difficult to deliver