Impact of Revi® Implantable Tibial Neuromodulation on Quality of Life in Patients with Urgency Urinary Incontinence

Abstract

Introduction and Hypothesis

The objective was to evaluate quality-of-life (QoL) improvements following Revi® implantable tibial neuromodulation (ITNM) in patients with urgency urinary incontinence (UUI).

Methods

This prospective, multicenter study evaluated the Revi® System, an ITNM device that allows for at-home therapy using an external, battery-operated unit. The primary efficacy and safety endpoints were assessed at 6 and 12 months; thereafter, participants either exited the study or consented to extend follow-up. This completers analysis evaluated QoL outcomes using the Overactive Bladder Questionnaire (OAB-q) and the total transformed Health-Related QoL (HRQL) score through 24 months.

Results

Subfascial implantation of the Revi System was performed in 151 participants. Primary efficacy and safety endpoints were met and no device- or procedure-related serious adverse events occurred. Consistent QoL benefits were seen throughout 24 months, with clinically significant (≥ 10-point change) and sustainable improvements in symptom severity in all domains of the OAB-q and HRQL scores. Additionally, 96.8% reported treatment benefit, 96.7% reported satisfaction, and 100% reported a willingness to continue therapy at 24 months. Notably, among participants who did not meet the primary efficacy endpoint at 24 months (n = 20; 20.6%), appreciable therapeutic benefit was still noted; 83.3% reported treatment benefit, 66.7% reported satisfaction, and 100% reported a willingness to continue this therapy.

Conclusions

Revi is an effective and safe intervention for UUI. Two-year results of the Revi System demonstrate clinically meaningful and sustainable improvements to bladder-related and overall health-related QoL, including those whose objective benefit did not meet the primary efficacy endpoint.

Introduction

Overactive bladder (OAB) is a prevalent health issue characterized by urinary urgency, frequency, nocturia, and/or urgency urinary incontinence (UUI) [1]. Although OAB reportedly affects millions of individuals, published incidence rates for UUI are likely underestimated owing to patient embarrassment and denial [2, 3]. UUI can significantly impact many aspects of daily functioning, including reductions in social activity, physical activity, self-confidence, and intimacy, along with increased anxiety and depression [4, 5]. Consequently, UUI is commonly associated with decreased quality of life (QoL), an important metric that supports comprehensive quality of clinical care for patients [5].

Initial treatment strategies for UUI have included dietary, behavioral, and lifestyle modifications, pelvic floor physiotherapy and bladder re-training, and medications. The treatment landscape for UUI has continued to evolve, with greater appreciation for more advanced technologies, including neuromodulation [6]. The American Urological Society (AUA)/Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction (SUFU) Guidelines for OAB treatment were updated in 2024, supporting earlier consideration for minimally invasive procedural therapies in the treatment algorithm, including neuromodulation [7, 8]. Among treatment modalities, neuromodulation techniques have gained prominence as effective options, with the sacral or tibial nerves being targets [9]. The precise mechanisms responsible for the benefits observed in neuromodulation for UUI continue to be elucidated. Regardless, evidence supports the direct and indirect influence of nerve stimulation on neural pathways of the pelvic plexus that regulate bladder control, with over 20 years’ experience noting significant improvements in OAB/UUI and patient QoL [10].

Innovation-driven technological advancements in neuromodulation are proposed to further promote its utility and associated effectiveness and safety. Improved programming, customizable stimulation plans, remote patient care and monitoring, and nonsurgical options for battery management are a few of the more recent innovative developments. The Revi System is a FDA-cleared (2023) implantable tibial neuromodulation (ITNM) device indicated for the treatment of UUI. The pivotal Overactive blAdder StimulatIon System (OASIS) trial recently reported 24-month results of ITNM therapy using the Revi System [11]. The study met the primary efficacy and safety endpoints, demonstrating clinically significant and meaningful improvements in UUI at 6 months that have proven durable throughout the 24 months of follow-up. Further, UUI response rates at 6 months and 24 months were 76.4% and 79.4% respectively, with an excellent safety profile throughout the 24-month follow-up. Minimal data are available related to QoL improvements following ITNM. This secondary analysis of this pivotal OASIS Study summarizes the impact of the Revi System on QoL over 24 months.

Materials and Methods

The OASIS Study is a prospective, multicenter, single-arm, open-label, pivotal clinical trial evaluating the efficacy and safety of the Revi System (BlueWind Medical, Park City, UT, USA) in adult females with UUI (OAB-wet). Several QoL questionnaires were included in the OASIS Study (see the Study Design section below).

Study Participants

Inclusion/exclusion criteria have been previously described [11, 12]. Participants were enrolled with a confirmed diagnosis of refractory UUI, defined as 7 consecutive days with ≥ 9 UUI leaking episodes, and ≥ 1 UUI episode per day over 5 consecutive days. Participants were “refractory,” having previously demonstrated inadequate responses to conservative treatments yet were willing and able to perform a patient-controlled therapy. Participants with OAB symptoms associated with underlying neurological pathological conditions and/or neurogenic bladders were excluded. Stress-predominant urinary-incontinent patients were also excluded.

A total of 23 centers throughout the USA, the UK, the Netherlands, and Belgium enrolled participants into the study. Ethics committee/IRB approvals were obtained for all participating centers. This study was conducted in compliance with the study protocol, Good Clinical Practice guidelines, the guidelines to the Declaration of Helsinki, and all other applicable regulatory requirements.

Study Design

As previously described [11, 12], the implant was placed subfascially under local anesthesia in a small incision (~ 5 cm) in the lower leg immediately above the medial ankle. After initial wound healing, the implant was activated wirelessly and participants have been followed up to the 24-month timepoint. On-going observation up to 36 months is underway.

Participant demographics and baseline characteristics were recorded during screening. The primary efficacy endpoint was defined as a responder rate, a percentage of those achieving ≥ 50% improvement in UUI episodes at 6 months. Participants completed voiding diaries at 1, 3, 6, 9, 12, 18, and 24 months. Voiding diaries at baseline, 6 months, and 12 months were 7-day diaries, whereas all others were 3-day diaries. Use of 3-day diaries was considered appropriate for most follow-up visits based on a prior comparison between 3-day and 7-day diaries [13].

Secondary outcomes employed validated QoL questionnaires (Overactive Bladder Questionnaire [OAB-q, gauging HRQL and symptom severity], Patient Global Impression of Improvement [PGI-I, rating the response to a therapy], and Treatment Benefit, Satisfaction, and Willingness to Continue [, ascertaining the patient’s perception of a treatment’s effect in consideration of relative benefit, satisfaction, and intention or willingness to continue therapy]), collected at 6, 12, and 24 months. Participants were contacted by phone at 18 months. Treatment satisfaction and any changes to the participants’ treatment regimen were discussed. Adverse events (AEs) were recorded from surgery throughout follow-up, and included the event’s relatedness, severity, and outcome. All AEs through 12 months were adjudicated by a Clinical Events Committee (CEC) and thereafter were adjudicated by site investigators. An independent Data and Safety Monitoring Board (DSMB) evaluated the safety, conduct, scientific validity, and data integrity of the study.

Neuromodulatory Stimulation with the Revi System

The Revi System includes an implant and wearable unit. The Revi System’s wearable unit transmits energy to the implant, which sends electrical pulses onto the tibial nerve (Fig. 1). Participants were asked to perform stimulation at home twice daily for ≥ 30 min (with a maximum of 2 h per day), for the initial 12 months. Participants who continued to long-term follow-up (i.e., the 12-month extension up to 24 months post-implant) were treated per physician recommendations (two or more 30-min sessions per week).

Fig. 1.

Implantable tibial neuromodulation treatment with the Revi System. Components of the Revi® System include the active implantable unit, an external wearable unit that magnetically couples to the implant when the system is in use, and a clinician programmer. RF radiofrequency

Statistical Analysis

This completers’ analysis of QoL outcomes from the OASIS Study dataset includes all data available through the 24-month timepoint. Study endpoints and statistical methods have been previously described [11, 12]. At 24 months, trial endpoints included frequency of UUI episodes (based on a 3-day voiding diary), QoL and patient satisfaction measures, and incidence of device- or procedure-related AEs. The current analysis evaluated secondary and additional efficacy endpoints of OAB-q, PGI-I, and benefit, satisfaction, and willingness to continue (BSW) scores. Data were analyzed for counts and percentages for categorical baseline variables, with standard deviation (SD) or standard error (SE) reported as noted. Analyses were generated using SAS Version 9.4 (SAS Analytics, Cary, NC, USA).

Results

Efficacy and safety results from the 24-month evaluation have been previously described [11]. The current report extends these findings to include long-term evaluation on multiple measures of QoL and patient satisfaction.

Participant Characteristics

The study enrolled 151 women; 95.4% were white, the mean age was 58.8 years (SD 12.5), and BMI was 30.2 kg/m² (SD 6.9). The average number of UUI episodes per day at baseline was 4.8 (SD 2.9) with 0.9 large leaks per day (SD 1.7), and a frequency of 10.0 voids per day (SD 3.3). Most participants had a mean time since OAB diagnosis of > 5 years (64.2%) and almost all participants (99.3%) had a history of prior medication use for OAB (Table 1). As previously reported, 32.7% of participants were using OAB medication at baseline; participants were instructed to remain on stable doses of OAB medications for the first 12 months of follow-up [12].

Table 1.

Participant characteristics

Characteristic	Data
Implanted participants, N	151
Demographics, mean (SD)
Age (years)	58.8 (12.5)
BMI (kg/m2)	30.2 (6.9)
OAB symptom burden, mean (SD)
UUI episodes (per day)	4.8 (2.9)
Large leaks (per day)	0.9 (1.7)
Frequency	10.0 (3.3)
Race, % (n/N)a
Black/African American	3.4 (3/87)
White	95.4 (83/87)
Other	1.1 (1/87)
Ethnicity, % (n/N)
Hispanic or Latino	6.9 (6/87)
Not Hispanic or Latino	93.1 (81/87)
Time since OAB diagnosis, % (n/N)b
< 6 months	1.3 (2/151)
6 months to 1 year	4.6 (7/151)
1 to 5 years	29.1 (44/151)
> 5 years	64.2 (97/151)
Previous use of OAB medication, % (n/N)	99.3 (150/151)
Geography, % (n/N)
USA	57.6 (87/151)
Europe	42.4 (64/151)

BMI body mass index, OAB overactive bladder, SD standard deviation, UUI urge urinary incontinence

^aRace and ethnicity was reported for US participants only

^bTime since OAB diagnosis as reported at the time of initial study enrollment

At 24 months, 97 participants had data available for analysis. Participant discontinuation past the 12-month timepoint was largely attributed to the delayed start of the extension study. Baseline characteristics and response rate of the populations active at 6 months and 24 months of follow-up were similar, indicating that results at 24 months are representative of the overall OASIS Study population (Table 2).

Table 2.

Population comparison of participants enrolled at 6 months and 24 months. Baseline characteristics and response rate of the populations active at 6 months and 24 months of follow-up were very similar, indicating that results at 24 months are representative of the overall Overactive blAdder StimulatIon System (OASIS) study population

Parameter	OASIS 6 months (N = 144)	OASIS 24 months (N = 97)
Baseline UUI, mean (SD)a	4.8 (3.0)	4.5 (2.6)
Baseline voids, mean (SD)	10.1 (3.3)	10.1 (3.0)
Baseline OAB-q, mean (SD)b	47.1 (19.6)	47.6 (19.8)
Age, mean (SD)	59.0 (12.5)	59.8 (11.8)
Responders at 6 months, % (n/N)	77.8 (112/144)	82.5 (80/97)
Therapy response at each endpoint, % (n/N)c	77.8 (112/144)	79.4 (77/97)

^aBaseline urgency urinary incontinence (UUI) = average number of urgency-related incontinence episodes at baseline

^bOveractive Bladder Questionnaire (OAB-q) Health-Related Quality of Life (HRQL) total transformed score. Note: two participants were missing baseline OAB-q scores at baseline; available data have been reported

^cCompleters analysis

Summary of Efficacy and Safety Outcomes

The primary efficacy endpoint at 6 months of > 50% improvement in UUI episodes was achieved by 76.4% (p < 0.0001) of participants, which was sustained over 24 months (12 months, 82.0%; 24 months, 79.4%), as described in previous publications [11, 12]. Importantly, no device- or procedure-related serious AEs occurred through 24 months. A very low rate of device explantation (n = 3; 2.0%) was reported, and no device migrations or surgical revisions were required.

Overactive Bladder and Health-Related Quality of Life

The OAB-q showed clinically impactful (≥ 10-point change) [14, 15] and sustainable improvements in symptom severity (transformed score) and HRQL, including total HRQL as well as all independent domains (i.e., coping, concern, sleep, social domains) at all timepoints following ITNM (Fig. 2, Table 3). Symptom severity (transformed score), which shows improvement when the score decreases, was reduced from 70.3 (n = 149; SD 16.0) to 32.4 (n = 144; SE 1.7), 30.6 (n = 139; SE 1.8), and 31.5 (n = 96; SE 2.1) at 6 months, 12 months, and 24 months respectively, indicating a noteworthy ~40-point change. HRQL (transformed score), which increases with improvement up to a maximum of 100, was improved from 46.6 (n = 149; SE 1.61) to 81.1 (n = 144; SE 1.4), 81.8 (n = 139; SE 1.7), and 83.3 (n = 96; SE 1.9) at 6 months, 12 months, and 24 months respectively, a > 30-point change. Overall, clinically meaningful QOL improvements (≥ 10-point change in total transformed HRQL score) were reported in 83.1% (n = 142), 85.4% (n = 137), and 87.2% (n = 94) of participants at 6, 12, and 24 months respectively.

Fig. 2.

Implantable tibial neuromodulation treatment with the Revi System improves Overactive Bladder Questionnaire outcome Measures. Clinical improvements were observed in A symptom severity, B Health-Related Quality of Life (HRQL) Total Score, and individual domains for C coping, D concern, E sleep, and F social parameters. Data are presented as the mean ± standard error

Table 3.

Implantable tibial neuromodulation treatment with the Revi System improved quality-of-life outcomes

Outcome measure	0 months	6 months	12 months	24 months
BSW, % response	–	N = 141	, N = 138	, N = 94
Benefit from treatment	–	95.7	94.9	96.8
Satisfactiona	–	93.8	95.4	96.7
Willingness to continue	–	96.8	96.7	100.0
PGI-I, % response		N = 141	N = 139	N = 97
No change or worse	–	5.0	6.5	3.1
A little better	–	24.8	15.1	16.5
Much better	–	37.6	38.1	44.3
Very much better	–	32.6	40.3	36.1
OAB-q	N = 149	N = 141	N = 139	N = 96
Independent domains, % response
Coping	35.1 (1.8)	76.6 (2.0)	77.5 (2.1)	80.2 (2.3)
Concern	40.8 (2.1)	80.0 (1.7)	81.3 (1.8)	81.2 (2.1)
Sleep	47.7 (2.1)	77.9 (1.8)	77.7 (2.0)	78.6 (2.4)
Social	72.2 (2.0)	93.6 (1.1)	93.2 (1.3)	95.7 (1.5)
OAB-q Symptom Severity Score (transformed), mean (SE)	70.3 (1.3)	32.4 (1.7)	31.0 (1.8)	31.0 (2.1)
HRQL total score (transformed), mean (SE)	46.6 (1.6)	81.1 (1.4)	81.8 (1.7)	83.3 (1.9)

BSW benefit, satisfaction, and willingness to continue, HRQL health-related quality of life OAB-q Overactive Bladder Questionnaire, PGI-I Patient Global Impression of Improvement SE standard error

^aBSW satisfaction scores were analyzed for 6-month, 12-month, and 24-month timepoints from 129, 130, and 91 participants respectively

Patient Global Impression of Improvement

The vast majority of participants reported significant symptom improvements utilizing the PGI-I (i.e., very much better, much better, and a little better) following treatment with ITNM at each timepoint (95.0% at 6 months, n = 141; 93.5% at 12 months, n = 139; 96.9% at 24 months, n = 97). A higher frequency of responses favored “very much better” and “much better” compared with “a little better” across timepoints (Table 3), with 70.2% (n = 99), 78.4% (n = 109), and 80.4% (n = 78) at 6 months, 12 months, and 24 months respectively reporting these responses.

Benefit, Satisfaction, and Willingness to Continue

Nearly all participants who completed follow-up through 24 months reported treatment benefit, satisfaction, and a willingness to continue ITNM treatment with the Revi System, first at 6 months and sustainable through 24 months. BSW assessment demonstrated treatment benefit (95.7% at 6 months; 94.9% at 12 months; 96.8% at 24 months), satisfaction with the treatment (93.8% at 6 months; 95.4% at 12 months; 96.7% at 24 months), and a willingness to continue therapy (96.8% at 6 months; 96.7% at 12 months; 100% at 24 months; Table 3).

Quality-of-Life Outcomes in Participants Without ≥ 50% Reduction in Urge Urinary Incontinence Episodes

Importantly, within the subset of participants who did not meet the efficacy endpoint at 24 months (20.6%; n = 20), many reported positive improvements in QoL outcomes, indicating potential benefits of therapy even when the efficacy endpoint of ≥ 50% reduction in UUI episodes was not reached. Within this group of participants, 18 completed the BSW; treatment benefit was acknowledged in 83.3% (n = 15), 66.7% (n = 12) reported satisfaction, and 100% (n = 18) reported a willingness to continue therapy (Fig. 3). To elucidate potential explanations for such responses, impact on voiding diary outcomes within this group were further explored. Among these 20 participants, the mean reduction in UUI episodes was 20.3%, with 55% (n = 11) of participants reporting a ≥ 25% to < 50% reduction in UUI episodes. Large leaks, a subset of leaks with higher impact on QoL [16], were reported in 17 of these participants at baseline and the majority, 58.8% (n = 10), reported no large leaks in their 24-month voiding diaries, illustrating other ways in which therapy may result in impactful changes, improving QoL.

Fig. 3.

Implantable tibial neuromodulation treatment with the Revi System improves benefit, satisfaction, and willingness to continue (BSW) in cohort of urge urinary incontinence (UUI) nonresponders (< 50% reduction). A At 24 months, a total of 21.6% of participants did not meet the primary endpoint and showed < 50% reduction in UUI episodes. B The majority of this participant cohort showed treatment benefits, satisfaction, and were willing to continue treatment. Tx treatment

Safety Outcomes

A total of 414 AEs were reported during the 24-month period, including 7 device-related AEs and 18 procedure-related AEs. All AEs were considered mild to moderate in severity with no device- or procedure-related serious AEs observed. Few explants occurred (2%; 3 out of 151), and were unrelated to device- or procedure-related AEs. There were no device migrations or revision procedures. A favorable benefit to risk and overall safety profile was observed.

Discussion

The OASIS 24-month trial findings support improvement in UUI episodes across multiple QoL and satisfaction outcome measures. This analysis focused on QoL assessments in women with UUI treated with ITNM using the Revi System. A previous report demonstrated positive efficacy for UUI episodes, with 79% of participants noting a ≥ 50% improvement in UUI at the 24-month timepoint, and 56% experiencing ≥ 75% improvement [1]. This report expanded on these findings with clinically meaningful benefits seen across multiple measures of QoL that were sustained throughout the treatment duration.

The QoL assessments utilized in the current study are all validated and commonly used in patients with UUI. These assessments go beyond the standard physical measure of UUI and add to the comprehensive evaluation of the personal experience. Prior reports show low QoL associated with OAB and significant influence on physical, mental, occupational, sexual, and social health domains impacting many aspects of daily living [5, 17, 18]. Patients often impose limitations on their activities and feel shame about their condition, highlighting significant QoL changes for these individuals. It has been proposed that in this patient population, interventional outcome measures should also reflect patient experience and QoL perception as these outcomes are of utmost importance to patients [19].

In this study, burden on QoL was alleviated with significant improvements in OAB-q symptom severity, independent HRQL domains (i.e., coping, concern, sleep, and social), total HRQL, PGI-I, and positive BSW following treatment with the Revi System, in parallel to UUI improvements. The minimally important difference (MID) recommended for the OAB-q and all subscales is a ten-point change post-treatment [14]. ITNM treatment improved all domains by at least 20 points at the 24-month timepoint, with a mean change of 35 points in the overall HRQL score. Notably, improvements in all QoL measures were reported at the first timepoint (6 m) and sustained throughout the current study duration of 24 m. Furthermore, participants who did not meet the primary UUI efficacy endpoint were still afforded meaningful improvements in QoL, demonstrating clinical benefit impacting patient status in multiple areas. Collectively, these QoL outcomes demonstrate a positive, robust, and lasting response following ITNM treatment with the Revi System.

A recent systematic review and meta-analysis reports on a variety of efficacy and safety outcomes following sacral neuromodulation (SNM) and ITNM in OAB [20]. Reductions in UUI episodes and OAB symptoms, significant improvements in QoL, and low rates of procedure- and device-related AEs were reported across multiple systems. The current results are similar to these findings and demonstrate that SNM QoL improvement scores are generally lower than those for ITNM. Comparison with the weighted average of the proportion of patients with improvement of ≥ 10 points in HRQL (SNM, 48.4%), PGI-I improvements (SNM, 74.9%), and therapy satisfaction (SNM, 75.5%) was generally lower than the improvements observed in the current report using ITNM treatment with Revi [20]. Unique system specifications and treatment applications may account for these differences between studies.

The favorable safety profile, with a 2% explant rate and low AE rates, highlights another advantage of using the Revi System. The implant is anchored into place using direct fascia suturing, thereby reducing the risk of migration. The non-implantable wearable battery reduces the need for surgical reintervention. Additionally, the ability to individualize stimulation parameters helps to optimize patient response, further enhancing the therapy's adaptability over time. Clinical improvements continued to be observed when flexibility regarding the frequency of stimulation treatment sessions increased after the first 12 months. Sustained benefits through 24 months in this context provide confidence in treatment flexibility amenable to real-world living.

The findings of this study should be interpreted with consideration of the limitations. The OASIS study did not include randomization or a control arm to assess for placebo effect owing to the inability to adequately blind patients to the stimulation. However, the extended follow-up evaluation over 24 months has demonstrated consistent improvements across multiple efficacy and QoL measures, reducing the potential for any bias from a placebo effect. In the future, the authors plan to further elucidate device0use patterns and their potential impact on efficacy, as well as to analyze any changes in OAB medication use during long-term follow-up through 36 months.

An additional limitation is the loss to follow-up experienced after the initial 12-month study owing to several patients exiting the study prior to the initiation of enrollment in the extension study. However, the populations that completed the initial 6-month and final 24-month assessments were similar, supporting the notion that results at 24 months are representative of the overall study population. In addition, the loss to follow-up prior to initiation of the extension study was not as extensive as that in the STEP study’s 24-month results [21]. Interestingly, 80% (n = 20) of the participants who did not meet the primary efficacy endpoint at 12 months (the conclusion of the initial consented study) still elected to continue with the long-term follow-up, likely influenced by the improved bladder- and health-related QoL factors described in this manuscript. Nevertheless, despite some participant drop-off, data availability at the extended timepoints is consistent with that of other trials of similar duration.

With regard to potential or perceived conflicts of interest (COI) due to the educational and surgical training consulting activities of the authors, we do not believe that these introduced bias into any of the outcomes of the OASIS study or any of the subsequent reporting. These relationships did not influence the design, conduct, or reporting of the study. As is expected with all industry-led studies, all sites were compensated for all study-related costs by BlueWind Medical. Furthermore, although an employee of BlueWind Medical authored the first draft of this manuscript to ensure protection of commercially valuable intellectual property, this first draft primarily only summarized the study methods and outcomes. The investigator authors completed interpretation of the results and conclusions to ensure that the appropriate scientific rigor was applied, and all relevant safety concerns were addressed. The investigator authors were not compensated for interpreting, writing, or reviewing the manuscript.

Conclusions

Implantable tibial neuromodulation with the Revi® System represents a highly effective treatment modality for UUI that accordingly results in clinically meaningful and sustainable improvements in both bladder-related and overall health-related QoL. These important QoL improvements were seen within 6 months of implant activation and were sustained through 24 months. Furthermore, similar clinically meaningful QoL improvements were noted even in those who did not meet the initial primary efficacy endpoint of ≥ 50% improvement in their UUI; the improvements noted were deemed worthy of continued ITNM therapy by the participants. Continued follow-up of the OASIS Study to 36 months is currently underway, assessing even longer-term efficacy, safety, and QoL.

Authors’ Contributions

Protocol/project development: J.P.F.A.H., R.R.D.; data collection or management: J.P.F.A.H., K.L.F., R.R.D., S.E.S.; data analysis: R.R.D., S.E.S.; manuscript writing/editing: S.E.S., J.P.F.A.H., K.L.F., R.R.D.

Funding

The OASIS Trial was funded by BlueWind Medical.

Declarations

Study Registration

Investigational device exemption (IDE) # G200013. ClinicalTrials.gov Identifier: NCT03596671.

Disclosures

J.P.F.A.H., S.E.S., K.L.F., and R.R.D. reported being paid consultants for BlueWind Medical. The authors declare that these relationships have not influenced the design, conduct, or reporting of the study.

An employee of BlueWind Medical authored the first draft of this manuscript to ensure protection of commercially valuable intellectual property; this first draft primarily consisted of summarizing the study methods and outcomes. The investigator authors listed above completed the results interpretation and conclusions to ensure that the appropriate scientific rigor was applied and relevant safety concerns were addressed. The investigator authors listed above were compensated for their participation in the study in that all study-related costs were covered by BlueWind Medical; but not for their time writing or reviewing the manuscript.

IRB Approval

The following lists all sites and details for Institutional Review Board (IRB) approval to participate in this study:

Investigational site	IRB chairperson	Principal investigator	IRB address
Sanford	Donald A. Deieso Ph.D	Dr. Kevin Benson	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Adult & Ped UroGyn	Donald A. Deieso Ph.D	Dr. Becky McCrery	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Chesapeake Urology RA/Owing Mills	Donald A. Deieso Ph.D	Dr. Laura Giusto	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
University of Washington	Donald A. Deiseso Ph.D	Dr. Suzette Sutherland	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Southern UroGyn	Beverly Daniel, MD	Dr. Andrea Pezzella	Lexington Medical Center IRB 2720 Sunset Blvd, West Columbia, SC, 29169, USA
Gulf Coast Clinical TrialAssociates	Donald A. Deieso Ph.D	Dr. Osvaldo Padron	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Minnesota Urology	Donald A. Deieso Ph.D	Dr. Michael Ehlert	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Duke Urogynecology	Donald A. Deieso Ph.D	Dr. Cindy Amundsen	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Inova Fairfax Medical	Donald A. Deieso Ph.D	Dr. Abbas Shobeiri	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Chesapeake Urology RA, Hanover	Donald A. Deieso Ph.D	Dr. Kaiser Robertson	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
University of California, Irvine	Donald A. Deieso Ph.D	Dr. Felicia Lane	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Comprehensive Urological Care	Donald A. Deieso Ph.D	Dr. Ning Wu	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Norwalk Urology	Donald A. Deieso Ph.D	Dr. Scott Serels	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Colorado Pelvic Floor Consultants	Donald A. Deieso Ph.D	Dr. James Lukban	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Kaiser Permanente	Dr. Eric Macy	Dr. Kimberly Ferrante	Kaiser Permanente Southern California Institutional Review Board 393 E. Walnut St., 4th Floor Pasadena, CA, 91188, USA
Northshore Medical Group	Donald A. Deieso Ph.D	Dr. Ghazaleh Rostami Nai	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
Regional Urology	Donald A. Deieso Ph.D	Dr. Kevin Cline	Western Institutional Review Board 1019 39th Ave SE, Suite 120, Puyallup, WA, 983374, USA
University of Antwerp	Prof. Dr Peter Michielsen	Dr. De Wachter	Ethics Committee of UZ Antwerpen UZA (Universitair Ziekenhuis Antwerpen [Antwerp University Hospital]), Wilrijkstraat 10, 2650 Edegem, Belgium
University of Leuven	Prof. Dr. Minne Casteels	Prof. De Ridder	Heilig Hart Ziekenhuis Lier Mechelsestraat 24, 2500 Lier, Belgium
Munich ISAR Klinik	Prof. Dr.med.Dieter Luft	Prof. Dr Ursula Peschers	Universitätsklinikum Tübingen, Geissweg 3, 72076 Tübingen, Germany
Saint Mary’s Hospital	Koula Asimakopoulou	Dr. Alex Digesu	London–Bromley Research Ethics Committee, Temple Quay House, 2 The Square, Temple Quay, Bristol, BS1 6PN, UK
Birmingham Women’s Hospital	Koula Asimakopoulou	Dr. Philip Tooz-Hobson	London–Bromley Research Ethics Committee, Temple Quay House, 2 The Square, Temple Quay, Bristol, BS1 6PN, USA
Radboud University Medical Center	Dr. R.B. Keus	Dr. Frank Martens	Radboud universitair medisch centrum Concernstaf Kwaliteit en Veiligheid Commissie Mensgebonden Onderzoek Regio Arnhem-Nijmegen, Postbus 9101, 6500 HB Nijmegen, Netherlands Huispost 628, Geert Grooteplein 10 Radboudumc hoofdingang, route 629
Maastricht University	Dr. R.B. Keus	Dr. Martijn Smits	Radboud universitair medisch centrum Concernstaf Kwaliteit en Veiligheid Commissie Mensgebonden Onderzoek Regio Arnhem-Nijmegen, Postbus 9101, 6500 HB Nijmegen, Netherlands Huispost 628, Geert Grooteplein 10 Radboudumc hoofdingang, route 629
Rijnstate Hospital	Dr. R.B. Keus,	Dr. Michael van Balken	Radboud universitair medisch centrum Concernstaf Kwaliteit en Veiligheid Commissie Mensgebonden Onderzoek Regio Arnhem-Nijmegen, Postbus 9101, 6500 HB Nijmegen, Netherlands Huispost 628, Geert Grooteplein 10 Radboudumc hoofdingang, route 629
UMC Utrecht	Dr. R.B. Keus	Dr. Jetske van Breda	Radboud universitair medisch centrum Concernstaf Kwaliteit en Veiligheid Commissie Mensgebonden Onderzoek Regio Arnhem-Nijmegen, Postbus 9101, 6500 HB Nijmegen, Netherlands Huispost 628, Geert Grooteplein 10 Radboudumc hoofdingang, route 629
Isala	Dr. R.B. Keus,	Dr. Bart Witte	Radboud universitair medisch centrum Concernstaf Kwaliteit en Veiligheid Commissie Mensgebonden Onderzoek Regio Arnhem-Nijmegen, Postbus 9101, 6500 HB Nijmegen, Netherlands Huispost 628, Geert Grooteplein 10 Radboudumc hoofdingang, route 629

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