The pivotal study of a coin-sized implantable tibial neurostimulator (eCoin device) aims to show safety and effectiveness of the study device for treatment of urgency urinary incontinence.

This is a prospective, single-arm study enrolling up to 135 human subjects across 15 sites in the United States with overactive bladder syndrome primarily focusing on the symptom of urgency urinary incontinence (UUI). Subjects enrolled had at least 1 UUI episode daily on a 3-day voiding diary, and were intolerant or showed an inadequate response to at least 1 second or third-line therapy prior to enrollment with the exception of prior sacral neuromodulation therapy. Subjects were washed off any overactive bladder medication (2 weeks), onabotulinumtoxinA (9 months), or percutaneous tibial nerve stimulation therapy (1 month). Subjects with lower leg conditions posing a higher risk of poor wound healing, neurogenic bladder, bladder pain syndrome, >1/3 stress urinary incontinence (SUI) episodes, or retention (PVR >150cc) were excluded.

The eCoin device is a flat and leadless neurostimulator containing a primary cell battery with an average operating life of 3 years. A conically shaped field of stimulation radiates from a center cathode to an anode outer rim of the 23.3 mm diameter and 2.4mm thick coin-sized and shaped device. The eCoin device was implanted subcutaneously above the fascia utilizing only local anesthetic. Following the procedure, the incision was covered for several days, a shower bag was worn during bathing for 2 weeks, flat footwear was worn for 4 weeks, and vigorous ankle movement (i.e. running, cycling) was restricted for 8 weeks to mitigate device migration prior to encapsulation.  The eCoin device was activated after an approximate 4-week healing period.  Automated low-duty stimulation of 30 minutes duration was thereafter provided every 3 days for the first 18 weeks then every 4 days without subject involvement. The subjects were followed for 48 weeks post-activation. Follow up visits occurred at 4, 8, 12, 24, and 48 weeks post-activation and included the collection of a 3-day voiding diary; completion of an Overactive Bladder Questionnaire (OABq), Patient Global Impression of Improvement in Incontinence (PGI-I), and satisfaction questionnaires; and assessment of adverse events.

This study was conducted in compliance with FDA and International Conference on Harmonization regulations for Good Clinical Practice. The Western Institutional Review Board approved the protocol and informed consent forms, and regulatory bodies in the United States approved conduct of study. All participants provided informed consent.

The study includes 133 subjects who were enrolled and implanted with the eCoin device during a 7-month period (9 urogynecologists and 6 urologists). Utilizing a Mayo tray with provided materials for implant and without reliance on imaging or interrogation of the device, implantation took an average of 21 minutes. The subject population had a mean age of 63.9 (11) and BMI of 30.4 (9.1). Most subjects were female (98.5%) and Caucasian (84.21%).  Baseline mean UUI episodes were 4.28 (3.08), and baseline mean OABq symptom bother and quality of life scores were 65.7 (30.0) and 45.7 (22.6), respectively.

After 36 weeks, outcome data are available on 122 subjects. The mean change in daily UUI episodes compared to baseline was -2.73 (-3.24, -2.22) (P<0.001), and the proportion of subjects in whom UUI episodes decreased by at least 50% (the “responder rate”) was 72.95% (95% CI, 64.16, 80.59). Additionally, 49.18% (95% CI, 40.02, 58.38) of subjects UUI episodes decreased by at least 75% and 30.33% (95% CI, 22.33, 39.30) were dry (100% decrease of UUI episodes). On the PGI-I scale, 77% of subjects reported feeling at least “better” and 36.89% of subjects reported feeling “very much better.”  OABq symptom bother scores improved significantly by -36.2 (95% CI, -41.2, -31.3) (P<0.001), and quality of life scores improved significantly by 35.9 (95% CI, 31.3, 40.7) (P<0.001). Subjects’ urinary incontinence episodes decreased significantly by 2.73 (95% CI, 1.04, 2.06) (P<0.001).  Figures 1 and 2 graphically depict subject responder rate and average UUI episodes at baseline, 12- 24- and 36-weeks post activation. Error bars in figure 2 indicate the 95% confidence interval for displayed UUI episode means.

Mild to moderate wound healing issues were seen in 12.8% of subjects. The majority resolved within 4 weeks with no effect on the subsequent therapy. Typically, minimal (i.e. ~5 mm) migrations of the device occurred prior to encapsulation with no significant correlation to efficacy. One related serious adverse event occurred with incision site infection prior to activation, which was managed with explant at a hospital with no long-term sequela.

133 of 137 (97%) enrolled patients were implanted with no exclusion based on a trial procedure or screening test. Patient reported outcomes align with objective voiding diary data, showing at the 36 week point 77% of subjects feeling at least better and a 72.95% responder rate pertaining to UUI. Similarly, the OABq shows subjects are experiencing clinically significant improvements in their quality of life and in their symptom bother score. Compared to baseline, patients experienced a dramatic and sustained reduction in UUI, as indicated by the significant decrease at 12-weeks post activation, with similar results maintained at 24- and 36-weeks post activation. The dry rate is high at 30.33%, particularly given the limited operator experience with the eCoin device. Additionally, the low incidence of temporary mild to moderate wound healing issues, presence of just one related serious adverse event, and an average implantation time of 21 minutes, suggest the procedure to implant the eCoin device is both safe and brief.

The study proved subcutaneous implantation of the eCoin device is easy to perform with minimal resources. Compliance with aftercare instructions provided to the patient was achieved without difficulty. Management of the device post-implant was seamless with no direct patient involvement, such as the use of a patient controlled remote for recharging or device powering. Once commercially available, eCoin implant and management is expected to be efficient from a workflow perspective. Clinically significant improvements in UUI, including an impressive dry rate and patient reported outcomes were shown. Such results obtained without a trial or screen test before implantation, and from urologist and urogynecologist investigators previously unfamiliar with the anatomy are very compelling. The results suggest that placement of the eCoin is less specific than placement of a sacral lead, though intuitively more specific than placement of a pulse generator. The eCoin device is a promising new therapy offering years of automated, sustained, desirable therapy for patients with overactive bladder syndrome.