Design of a Randomized Trial of Tibial Nerve Stimulator for Urgency Incontinence

Objectives: Tibial nerve stimulation (TNS) therapies offer an alternative treatment option for urgency incontinence (UUI). Implantable TNS devices may further advance the treatment landscape by offering targeted stimulation to patients at home. Here we describe the study design of an investigational, implantable ITNS device in patients with UUI with a projected battery life >5 years.

Methods: The study received investigational device exemption approval by the FDA (IDE# G190070) and IRB approval (wcg #20216197) and was registered on Clinicaltrials.gov (NCT05250908). This is a prospective, randomized, sham-controlled, double-blind, multi-center study of men and women with UUI being conducted at 25 sites in the United States and two sites in The Netherlands. Full inclusion/exclusion criteria can be found in Table 1. Implanting surgeons completed cadaveric training where surgical competence was assessed with surgical dissection by a trained anatomist.
A study flow diagram is presented in Figure 1. Immediately before the implant procedure, patients are randomized to ITNS-ON or ITNS-SHAM in a 2:1 ratio. All patients undergo surgical implantation of the ITNS device through a small incision. The stimulator lead is implanted adjacent to the tibial nerve, below the fascia, using ultrasound guidance. The pulse generator is housed in a pocket above the fascia. Patients randomized to ITNS-SHAM cross-over to ITNS-ON after assessment of the 3-month efficacy endpoints. The patient, investigator, and site staff are all blinded to treatment arm assignment. Total follow-up participation is 24 months.

Results: The study has two co-primary outcomes: 1) Response rate, defined as ≥50% reduction in UUI episodes recorded on bladder diaries, between ITNS-ON and ITNS-SHAM at 3 months; and 2) Response rate for all subjects from baseline to 12 months. Secondary outcomes include change in mean urgency score (calculated from the patients perceived level of urgency on the voiding diary), change in mean number of daily voids, and adverse events.
To have 90% power to detect a significant difference of ≥10% between treatment groups at a one-sided significance level of 0.025, a minimum of 180 (120 ITNS-ON; 60 ITNS-SHAM) subjects are required. Assuming an up-to 5% loss between randomization and 3-months provides a minimum total study sample size of 192.

Conclusions: This study will provide Level 1 medical evidence regarding the efficacy and safety of an implantable tibial nerve stimulator for the management of UUI.