Abraham Morse, MD, MBA
Harvard Medical School
Peters KM, Carrico DJ, Perez-Marrero RA, et al. Randomized trial of percutaneous tibial nerve stimulation versus Sham efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial. J Urol. 2010;183:1438-1443.
The SUmiT (Study of Urgent® PC vs Sham Effectiveness in Treatment of Overactive Bladder Symptoms) trial was a randomized, double-blind, multicenter trial that compared the efficacy of percutaneous tibial nerve stimulation (PTNS) to sham therapy in adults with overactive bladder.
Patients with overactive bladder were contributed by 23 geographically diverse centers in the United States. Women and men greater than 18 years of age who met thresholds of urinary urgency and frequency were enrolled, and were required to be off all antimuscarinic agents for at least two weeks. Exclusion criteria included pregnancy, previous diagnosis of neurogenic bladder, previous use of Botox® in bladder or pelvic floor muscles, Interstim®, Bion®, and previous PTNS treatment. For the primary endpoint, responders were defined as subjects “reporting bladder symptoms as moderately or markedly improved on a 7-level GRA (global response assessment) at week 13 after completing 12, 30-minute, consecutive weekly intervention sessions.” Secondary endpoints included individual symptom components of the GRA (urgency, frequency, and urinary urge incontinence), voiding diary parameters, OAB-q scores, and SF-36 scores at week 13 compared to baseline.
All subjects had placement of PTNS electrodes in the standard position as well as transcutaneous electrical nerve stimulation (TENS) electrodes on the dorsal and ventral midfoot. For the subjects in the treatment group, the current level was adjusted based on the subject’s motor and sensory responses. For those in the sham group, the TENS unit provided similar sensations and motor responses without any stimulation of the tibial nerve.
A total of 110 subjects were randomized to each group with all subjects assessed for the primary endpoint on an intention to treat basis. 103 subjects in the treatment group and 105 subjects in the sham group were available for an analysis of primary and secondary endpoints. Females accounted for 79% of the subjects overall, and the mean age was 61 years. Results from the Week 13 GRA assessment showed that 55% of the subjects in the treatment group rated their improvement as moderate or marked; whereas only 21% of the subjects in the sham group rated their outcome as moderate or markedly improved (P < 0.001). Individual GRA symptom scales, voiding diary parameters, and OAB-q changes from baseline were all statistically significantly improved in the active treatment group versus the sham group. The PTNS group showed statistically significant improvements in the SF-36 physical domain compared to baseline while the sham arm did not show any statistically significant improvement. However, there was no statistically significant difference between the two treatment groups in SF-36 scores.
There were six adverse events – (none serious) - in the PTNS group, including bruising, discomfort at the needle site, bleeding at the needle site, and leg tingling. There were no adverse events reported in the sham group.
This study used an innovative stimulation system that allowed for a reasonably realistic sham intervention. The trial results showed clinically significant differences in the proportion of patients who reported improvements in overactive bladder symptoms, voiding diary parameters, and disease specific quality of life in the treatment versus sham groups. The main weakness of the study is that the primary endpoint is based on the GRA, which does not appear to have published psychometric assessments (although the GRA has been used in other studies on lower urinary tract symptoms; mostly in the area of interstitial cystitis/painful bladder syndrome). In addition, the effectiveness of treatment was measured immediately after the cessation of weekly treatments and thus the long term sustainability of the improvements was not addressed, but is reported in a subsequent paper which is reviewed below.
Peters KM, Carrico DJ, MacDiarmid SA, et al. Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation: 24-month Results of the STEP Study. Neurourol Urodyn. 2012 Jun 5. [Epub ahead of print]
The STEP (Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation) study was an immediate extension of the SUmiT Trial. The STEP study was designed to investigate the persistence of symptom improvement with a tapering treatment protocol in patients who responded positively to a 12-week course of weekly treatment with PTNS.
Subjects who were randomized to the active treatment (PTNS) arm of the SUmiT trial were offered the opportunity to enroll in a follow-up study of gradual tapering of PTNS treatments. The protocol included two treatments at 14-day intervals followed by two treatments at 21-day intervals, then one treatment at a 28-day interval. Following this taper, subjects entered a period of “personal treatment plan” that was developed by the site investigator. Subjects repeated the GRA instrument, voiding diaries, and OAB-q at six-month intervals. For subjects who discontinued participation before 24 months, the study utilized a last value carried-forward analysis.
Of the 103 subjects that completed the active PTNS treatment arm of the SUmiT trial, 60 met the criteria of “moderately or markedly improved” and were offered the opportunity to continue with the STEP study. Fifty patients consented to continue participation, and of these, 35 continued up to 24 months. After completion of the tapering protocol, subjects received a mean of 1.3 treatments/month (median 1.2, range 0.3-4.3). Improvements in symptoms and voiding diary parameters as well as OAB-q scores demonstrated sustained improvements at all assessment points up to 24 months. There were no reported treatment related adverse events.
The STEP study documents sustained improvement in overactive bladder symptoms and bother with a tapering and then “PRN” use of PTNS averaging 1.3 treatments per month over 24 months. The investigators report that 82% of the subjects who completed the study had persistent moderate or marked improvement compared with baseline. This extension of the SUmiT trial suggests that for patients who initially demonstrate significant improvement with PTNS, improvement can be maintained in > 80% of patients. The main weakness in this study is the use of last value carried forward method for imputing missing data in subjects who dropped out of the study. This carries a risk of bias and is not the current recommended best practice.