12 month patient reported outcomes of a fully-implanted, nickel sized and shaped tibial nerve stimulator for the treatment of overactive bladder syndrome with urgency urinary incontinence

English S1, Lucente V2, Kaaki B3, Gilling P4, Meffan P5, Clark M6, Sand P7, Sen S8, Rovner E9, MacDiarmid S10

Research Type

Clinical

Abstract Category

Overactive Bladder

PRIZE AWARD: Best in Category Prize - Overactive Bladder
Abstract 179
Overactive Bladder
Scientific Podium Short Oral Session 8
Wednesday 4th September 2019
14:30 - 14:37
Hall K
Clinical Trial Overactive Bladder Urgency Urinary Incontinence Quality of Life (QoL) New Devices
1.Canterbury Urology Research Trust, Christchurch, New Zealand, 2.Institute for Female Pelvic Medicine & Reconstructive Surgery, Allentown, Pennsylvania, USA, 3.Unity Point Health, Waterloo, Iowa, USA, 4.Tauranga Urology Research Ltd, Tauranga, New Zealand, 5.Roundhay Medical Centre, Nelson, New Zealand, 6.The Clark Center for Urogynecology, Newport Beach, California, USA, 7.Northshore University Health System, Skokie, Illinois, USA, 8.Stanford University, Stanford, California, USA, 9.Medical University of South Carolina, Charleston, South Carolina, 10.Alliance Urology Specialists, Greensboro, North Carolina, USA
Presenter
S

Sharon English

Links

Abstract

Hypothesis / aims of study
To evaluate the long-term safety and efficacy of the eCoin® tibial nerve stimulation to treat refractory urinary urgency incontinence (UUI) at 3 months with follow up through 12 months. The focus of this abstract is patient reported outcomes.
Study design, materials and methods
The long-term (12 month) study was a prospective, single-arm, open-label study including 46 participants with refractory UUI, conducted at multiple sites in the US and New Zealand. The eCoin® was implanted in the lower leg over the tibial nerve and activated after 4 weeks. Bladder diary data and validated quality-of-life instruments, collected at 3, 6 and 12 months post-activation, were compared to baseline.  The Incontinence Quality of Life (I-QOL) survey and the Patient Global Impression of Improvement (PGI-I) for incontinence were utilized as the quality of life instruments [1,2].  
The neuromodulation device was implanted subcutaneously in the medial lower leg during an office procedure under local anesthesia. It’s leadless, battery-powered, hermetically enclosed in a titanium case, and slightly larger than a United States nickel in diameter (23.3 mm versus 21.2 mm) and thickness (2.4 mm versus 1.95 mm). The materials in direct contact with tissue include platinum electrodes and a silicone elastomer jacket covering the titanium housing. A tight device pocket was created caudally, above the fascia and the incision was closed in multiple layers and dressed. Wound-care instructions were provided. 
The incision site was checked 2 weeks post-implantation and the device was activated and programmed 4 weeks post-implantation. After activation, electrical stimulation was delivered to the tibial nerve as a constant-current pulse (20 pulses per second; pulse width 0.2 ms) between a cathode on the bottom of the device and an anode ring around the outermost edge. The amplitude was set per patient preference. The implant then automatically provided 30-minute stimulation sessions every 2 days for 12 weeks and every 15 days thereafter.  
This study was conducted in compliance with FDA and International Conference on Harmonization regulations for Good Clinical Practice. The central Institutional Review Board approved the protocol and informed consent forms, and regulatory bodies in the United States and New Zealand approved conduct of study. All participants provided informed consent.
Results
A total of 46 patients were implanted with the device. The participant mean age was 63.4 ± 11.5 years and 45/46 participants were female. The mean procedure time, from incision to final suture, was 17.4 ± 6.7 min. Intention-to-treat data are presented herein with imputation required to handle missing data on three patients (two with inadequate baseline diaries and one explanted prior to device activation).  Mean imputation was applied to the former scenarios and last observation carry forward was applied to the latter scenario. 
The relative median change in UUI from baseline was 65% at 3 months and 68% at 12 months.  Overall, 30/46 participants (65%) experienced more than a 50% improvement in UUI at 12 months compared with 32/46 participants (70%) at 3 months. Of participants, 19/46 (41%) experienced at least a 75% improvement and 12/46 (26%) experienced 100% improvement at 12 months (versus 41% and 22% at 3 months).  
The mean I-QOL score at baseline was 45.4 ± 20.4, compared to 71.3 ± 20.8 at 3 months, 67.4 ± 23.7 at 6 months, and 64.6 ± 25.6 at 12 months. At 12 months, the I-QOL scores improved by a mean of 86%.  The number of patients experiencing at least a 10 point increase in I-QOL score from baseline to 12 months post-activation was 29, or 63% of all patients. 
The mean PGI-I (Likert 7-point maximum scale), was 5.4 ± 1.3 at 3 months. A total of 33/46 patients (72%) responded with scores ≥ 5 (better, much better, or very much better), consistent with the size of the responder population. Of the total cohort, 15 (33%) reported feeling “very much better” (the highest possible score of 7). The remaining 24% of participants rated themselves as “same” and only 4% rated themselves as “worse,” with no patients rating themselves as “much worse,” or “very much worse.” At 12 months, the mean PGI-I was 5.3 ± 1.1. A total of 32/46 patients (70%) responded with scores ≥ 5 (better, much better, or very much better). Of those, 10/46 patients (22%) reported feeling “very much better” (the highest possible score). At 12 months, 14/46 patients (30%) reported feeling “about the same” (score of 4) and no patients reported feeling “worse,” “much worse,” or “very much worse.”
There was a single related serious adverse event of severe cellulitis secondary to the provided ankle wrap. This event occurred prior to device activation and resulted in explantation of the device.
Interpretation of results
The proportion of patients reporting a 10 point increase in I-QOL score from baseline to 12 months post-activation and the proportion of patients reporting better, much better, or very much better in PGI-I score comports with voiding diary data. 
In particular, the number of patients who achieved a 10 point improvement in their I-QOL is nearly the same as the number who showed a 50% or better improvement in their UUI symptoms (29 versus 30 of 46 patients).
The proportion of patients scoring a 10 point or better increase in their I-QOL reduced slightly from 3 months to 12 months with 1 of 46 patients (2%) no longer reporting a 10 point improvement.  
Similarly, 72% of patients reported feeling better, much better, or very much better in their PGI-I at 3 months with similar findings (70%) through 12 months.  One fewer patient no longer reported feeling better at 12 months.  Again, the proportionate improvement in the patient reported outcome comports with voiding diary data and sustained results show durability of treatment effect.  
The authors believe the very slight regression from 3 to 12 months in responder rates for both patient reported outcomes and voiding diary data might be explained by the change in therapeutic schedule from 30 minute stimulation sessions every other day to sessions every 15 days. The authors note that the manufacturer of the study device has changed the device firmware such that more frequent stimulation sessions are delivered over the life of the device.  It is also possible that placebo effect explains the slight regression of effect from 3 to 12 months.  With only 1 to 2 patients responsible for the difference in responder rates in diary data and patient reported outcomes, this regression is of minimal significance.       
While the number of patients who reported benefiting from the study device may have regressed by up to 2 patients at 12 months, the number of patients who reported becoming dry increased by 2 patients at 12 months, indicating some patients continue to improve over the long-term.  Furthermore, the 86% improvement in mean I-QOL and 68% relative median change in UUI from baseline to 12 months indicates positive long-term results for the cohort.
Concluding message
With a focus on patient reported outcomes, the eCoin® device showed durable efficacy and safety through 12 months and is a promising new treatment option for refractory OAB.
References
  1. Patrick DL, Martin ML, Bushnell DM et al: Quality of life of women with urinary incontinence: further development of the incontinence quality of life instrument (I-QOL). Urology 1999; 53: 71.
  2. Tincello DG, Owen RK, Slack MC et al: Validation of the Patient Global Impression scales for use in detrusor overactivity: secondary analysis of the RELAX study. BJOG 2013; 120: 212.
Disclosures
<span class="text-strong">Funding</span> Valencia Technologies Corp. <span class="text-strong">Clinical Trial</span> Yes <span class="text-strong">Registration Number</span> Clinicaltrials.gov, NCT03029624 <span class="text-strong">RCT</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> Quorum Review IRB <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes