New Implantable Tibial Nerve Stimulation Devices: Review of Published Clinical Results in Comparison to Established Neuromodulation Devices

Figures & data

Figure 1 Percutaneous Tibial Nerve Stimulation (PTNS).

Figure 2 Anatomy of the posterior tibial nerve and a) positioning of the PTNS needle; b) the BlueWind RENOVA^TM device; c) the eCoin^TM device.

Notes: b)For details see http://www.bluewindmedical.com/bluewind-renova; c) For details see http://valenciatechnologies.com/.

Table 1 Study Results for OAB Treatment with BlueWind RENOVA^TM

Criteria	Baseline n=15	Results After 3 Months n=14	p-Value Compared to Baseline^c	Number of Patients with >50% Improvement of Symptoms
Number of Voids	11.8±3.5	8.1±2.0 (31.4%)^b	0.002	8/14 (57%)
Mean Micturition Vol (mL)	158.5±58.7	176.5±59.2 (11.4%)^b	0.041	–
Severe Urinary Urgency^a	6.5±5.1	2.0±2.1 (69.2%)^b	0.003	13/14 (93%)
Urinary Incontinence^a	7.2±5.0	3.72±3.7 (48.3%)^b	0.091	4/11 (36%)
Severe Incontinence^a	2.8±5.2	0.3±0.4 (89.3%)^b	0.017	5/7 (71%)
Mean Urine Loss (g)	243.1±388.2	38.9±55.4 (84%)^b	0.038	5/9 (56%)
ICIQ-FLUTS^d	18.9±6.9	12.3±5.5 (34.9%)^b	0.001	4/14 (29%)
UDI^e	112.5±43.6	64.4±48.3 (42.8%)^b	0.004	5/14 (36%)
PPBC^f	5.0±1.1	3.7±1.3 (26%)^b	0.002	3/14 (21%)

Notes: ^aAssessed by number of episodes/day. ^bPercent of improvement from baseline in respective criteria. ^cStatistical analysis performed with Wilcoxon sign ranked test. ^dICIQ-FLUTS consists of 12 questions on bladder filling, voiding, and incontinence. ^eUDI is a 19-question survey on symptoms associated with lower urinary tract dysfunction, obstructive/discomfort symptoms, irritative symptoms and stress symptoms. ^fPPBC is a global measure for patients with OAB. Data from van Breda et al.⁵

Table 2 Study Results for OAB Treatment with BlueWind RENOVA^TM

Criteria	Baseline n=34	Results After 6 Months n=34	p-Value Compared to Baseline^c	Number of Patients (n=34) with >50% Improvement of Symptoms
UF voids^a	12±0.5	9.4±0.5 (21.7%)^b	<0.05	–
UF voided volume (mL)	161.7±12.3	179.3±15.1(10.9%)^b	<0.05	–
UF urgency^a	7.5±0.8	3.8±0.7 (49.3%)^b	<0.05	–
UF Clinical Success	–	–	<0.01	23(66.7%)
UI leaks^a	6.6±0.8	3.9±0.7 (40.9%)^b	<0.05	–
UI leak severity	1.8±0.1	1.4±0.1 (22.2%)^b	<0.0.5	–
UI Clinical Success	–	–	<0.001	25 (70.6%)
HRQL	All subscales > suggested MID of 10 points	–	<0.0001	–

Notes: ^aAssessed by number of episodes/day. ^bPercent of improvement from baseline in respective criteria. ^cStatistical analysis performed with paired t-test. Data from Heesakkers et al.⁶

Abbreviations: UF, urinary frequency; UI, urinary incontinence; HRQL, health related QoL questions and symptoms severity scores; MID, minimally important difference.

Table 3 Major Clinical Results of OAB Treatment with eCoin

Criteria	Baseline n=46	Results After 3 Months n=46	Results After 6 Months n=46	p-Value Compared to Baseline^c	Overall Improvement Rate for 3 Months	Overall Improvement Rate for 6 Months
Urinary Incontinence^b	4.2	1.7 (59.5%)^a	1.5 (64.3%)^a	0.001	71% median reduction 21.7% dry	47.8% with at least 75% reduction 23.9% with complete cessation
Urinary Urgency^b	6.0	2.8 (53.3%)^a	3.2 (46.7%)^a	0.001	49.4% median reduction	43.4% median reduction
I-QOL^d	45.4±20.4	71.3±20.8 (58.9%)^a	67.4±23.7 (48.9%)^a	–	Improved an average of 25.9 points	3 times the MID
PGI-I^e	–	5.4±1.3	–	–	–	72% indicated improvement with scores ≥5

Notes: ^aPercent of improvement from baseline in respective criteria. ^bAssessed by number of episodes/day. ^cStatistical analysis done with Wilcoxon sign ranked test. ^dI-QOL = A self-reporting incontinence quality of life instrument. ^ePGI-I = Patient global assessment of improvement survey on 7-point Likert scale from 1 (very much worse) to 7 (very much better). Data from MacDiarmid et al.⁷

Abbreviation: MID, minimally important difference.

Table 4 Comparison of Main Clinical Results for Different OAB Therapies

	BlueWind	eCoin	Urgent-SQ^a	InterStim^b	Botox^c
Type of Treatment	Implantable PTNS	Implantable PTNS	PTNS	Sacral Neuromodulation	Injection
Timeline	6 Months n=34	6 Months n=46	6 Months n=8	6 Months	6 Months n=60
UF voids/day	9.4±0.5 (21.7%)^f	–	10.88 (24.3%)^f	8.2 (49.1%)^f	32.9±18.1^d (14.1%)^f
UI episodes/day	3.9±0.7 (40.9%)^f	1.5 (64.3%)^f	3.63 (60.8%)^f	2.3 (73.9%)^f	5.0±12.5^d (39%)^f
UI severity^e	1.4±0.1 (22.2%)^f	–	0.5 (55.6%)^f	0.7±1.5 (86.3%)^f	3.1±1.1 (18.4%)^f
UU episodes/day	3.8±0.7 (49.3%)^f	3.2 (46.7%)^f	Rated urgency with either frequency or incontinence	Rated urgency with either frequency or incontinence	21.9±22.1^d (27%)^f
I-QoL^g	Improvement in both ICIQ-FLUTS^h and HRQL^i scales	67.4± 23.7 (48.9%)^f	86.5 (34.9%)^f	Improvement in both HRQL^i and OABqol scales	Improvement in both CSQ-8^j and KHQ^k scales

Notes: ^aStudy taken from outside the time criteria; no new updated clinical results are available.¹⁷ bData taken from review articles presenting meta-analysis data of clinical studies.^3,12 cData taken from review articles presenting meta-analysis data of clinical studies.^18,19 dNumber of episodes in 72 hrs. ^eSeverity based off a categorical scale designed by each study with lower numbers being loss of urine droplets to higher numbers being small amount of urine loss to changing clothes because of urine loss. ^fPercent of improvement from baseline in respective criteria. ^gI-QoL = A self-reporting incontinence quality of life instrument. ^hICIQ-FLUTS consists of 12 questions on bladder filling, voiding, and incontinence. ⁱHRQL = Health-Related QoL questions and symptoms severity scores. ^jCSQ-8 = 8 questions about satisfaction of treatment. ^kKHQ = questionnaire that evaluates quality of life in patients with UI.

van Breda HMK, Martens FMJ, Tromp J, Heesakkers JPFA. A new implanted posterior tibial nerve stimulator for the treatment of overactive bladder syndrome: 3-month results of a novel therapy at a single center. J Urol. 2017;198:205–210. doi:10.1016/j.juro.2017.01.07828189576

 PubMed Web of Science ®Google Scholar

Heesakkers JPFA, Digesu GA, van Breda J, Van Kerrebroeck P, Elneil S. A novel leadless, miniature implantable tibial nerve neuromodulation system for the management of overactive bladder complaints. Neurourol Urodyn. 2018;37:1060–1067. doi:10.1002/nau.2340128892221

 PubMed Web of Science ®Google Scholar

MacDiarmid S, Staskin DR, Lucente V, et al. Feasibility of a fully implanted, nickel sized and shaped tibial nerve stimulatory for the treatment of overactive bladder syndrome with urgency urinary incontinence. J Urol. 2019;201:1–6. doi:10.1016/j.juro.2018.10.017

 Web of Science ®Google Scholar

van der Pal F, van Balken MR, Heesakkers JPFA, et al. Implant-driven tibial nerve stimulation in the treatment of refractory overactive bladder syndrome: 12-month follow-up. Neuromodulation. 2006;9:163–171. doi:10.1111/j.1525-1403.2006.00056.x22151641

 PubMed Web of Science ®Google Scholar

Sukhu T, Kennelly MJ, Kurpad R. Sacral neuromodulation in overactive bladder: a review and current perspectives. Res Rep Urol. 2016;8:193–199. doi:10.2147/RRU.S8954427822462

 PubMed Web of Science ®Google Scholar

Tutolo M, Ammirati E, Van der Aa F. What is new in neuromodulation for overactive bladder? Eur Urol Focus. 2018;4:49–53. doi:10.1016/j.euf.2018.04.01929773501

 PubMedGoogle Scholar

Hsiao SM, Lin HH, Kuo HC. Factors associated with therapeutic efficacy of intravesical onatotulinumtoxinA injection for overactive bladder syndrome. PLoS One. 2016;11(1):e0147137. doi:10.1371/journal.pone.014713726824901

 PubMed Web of Science ®Google Scholar

Muhlstadt S, Mischner S, Kranz J, et al. Quo vadis botulinum toxin: normative constraints and quality of life for patients with idiopathic OAB? Front Surg. 2018;5:61. doi:10.3389/fsurg.2018.0006130386782

 PubMed Web of Science ®Google Scholar