An implantable tibial neuromodulation system was associated with reductions in urge urinary incontinence episodes through 12 months in the single-arm TITAN 2 pivotal study.
The prospective, multicenter investigational device exemption study evaluated the Medtronic implantable tibial neuromodulation system in patients with overactive bladder and urge urinary incontinence (UUI) who had failed or could not tolerate at least 2 overactive bladder medications. The study enrolled 188 patients at 26 US sites; 126 underwent implantation, and 62 were screen failures.
The primary end point was the proportion of implanted patients with at least a 50% reduction in UUI episodes per day at 6 months. The trial met its primary objective, with 59% of implanted patients meeting the responder definition at 6 months. That rate exceeded a prespecified 40% performance goal, which the researchers said was based on lower confidence-bound estimates from sacral neuromodulation literature and aligned with the benchmark used in another implantable tibial neuromodulation pivotal study. The researchers also acknowledged that the 40% performance goal has not been widely used in other neuromodulation studies.
At 12 months, the responder rate was 61% in the all-implanted analysis. The 12-month estimate included imputation because missing data exceeded the study’s 5% threshold; a complete-case sensitivity analysis produced a similar 12-month responder rate.
Patients had a mean age of 63 years, 95% were female, and the mean body mass index was 35 kg/m2. Implant procedures were performed under local anesthesia in hospital operating rooms, ambulatory surgical centers, or outpatient clinic procedure rooms. The device was implanted subcutaneously above the deep fascia overlying the tibial nerve. Initial programming included 30 minutes of stimulation every other day, with amplitude set at a comfortable level.
Researchers also reported statistically significant improvements from baseline in UUI episodes per day, urinary frequency among patients with at least 10 voids per day at baseline, Urgency Perception Scale scores, and overactive bladder–related quality of life at 6 months. Improvements were maintained through 12 months.
Among the urinary frequency subgroup, which included 59 patients with at least 10 voids per day at baseline, mean voids per day decreased from 13 at baseline to 10 at 6 months. Mean overactive bladder quality-of-life scores improved by 27 points at 6 months and by 26 points at 12 months.
Patient-reported outcomes showed improvement on most measures, although satisfaction declined over time. At 6 months, 82% of patients reported improvement on the Patient Global Impression of Improvement scale, and 74% reported being satisfied. At 12 months, 80% reported improvement and 65% reported being satisfied. At both time points, 76% said they would recommend the therapy to a friend or family member. At 6 months, 67% of patients said they preferred the implantable therapy over their previous experience with overactive bladder medications, 22% had no preference, and 11% preferred medications.
Adverse device effects occurred in 20% of implanted patients through 12 months. These events were related to the device, procedure, therapy, or study aids and were all mild or moderate. The most common events were infection- and pain-related events. Seven percent of patients had procedure-related implant-site infections; 1 infection required uncomplicated explant, and the remaining infections resolved with antibiotics. Two adverse device effects led to explant. One serious adverse device effect, Clostridium difficile colitis in a 90-year-old woman, occurred before 6 months, was considered possibly related to perioperative antibiotics, and resolved.
The researchers noted uncertainty about optimal stimulation cadence and parameters. Although improvements were reported in urgency and urinary frequency, the researchers noted that US Food and Drug Administration approval was granted for UUI and that further research may clarify the clinical implications of the urgency and frequency findings.
In an editorial comment published with the study, Kenneth M. Peters, MD, of Oakland University William Beaumont School of Medicine and Corewell Health William Beaumont University Hospital, questioned whether above-fascia placement activates the tibial nerve as effectively as devices with electrodes placed at the nerve. He also noted that patient satisfaction declined from 74% at 6 months to 65% at 12 months and that only 67% of patients preferred the device over medications despite study eligibility requiring failure of 2 overactive bladder medications.
Dr. Peters wrote that above-fascia implantable devices should be evaluated in sham-controlled trials and called for an NIH-sponsored randomized, sham-controlled study comparing above- and below-fascia products.
Disclosures can be found in the study.
Source: The Journal of Urology