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The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment: ROSETTA trial.

ABSTRACT: We present the rationale for and design of a randomized, open-label, active-control trial comparing the effectiveness of 200 units of onabotulinum toxin A (Botox A®) versus sacral neuromodulation (InterStim®) therapy for refractory urgency urinary incontinence (UUI). The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment (ROSETTA) trial compares changes in urgency urinary incontinence episodes over 6 months, as well as other lower urinary tract symptoms, adverse events and cost effectiveness in women receiving these two therapies. Eligible participants had previously attempted treatment with at least 2 medications and behavioral therapy. We discuss the importance of evaluating two very different interventions, the challenges related to recruitment, ethical considerations for two treatments with significantly different costs, follow-up assessments and cost effectiveness. The ROSETTA trial will provide information to healthcare providers regarding the technical attributes of these interventions as well as the efficacy and safety of these two interventions on other lower urinary tract and pelvic floor symptoms. Enrollment began in March, 2012 with anticipated end to recruitment in mid 2014.

SUBMITTER: Amundsen CL

PROVIDER: S-EPMC3989885 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment: ROSETTA trial.

Amundsen Cindy L CL Richter Holly E HE Menefee Shawn S Vasavada Sandip S Rahn David D DD Kenton Kim K Harvie Heidi S HS Wallace Dennis D Meikle Susie S

Contemporary clinical trials 20140130 2

We present the rationale for and design of a randomized, open-label, active-control trial comparing the effectiveness of 200 units of onabotulinum toxin A (Botox A®) versus sacral neuromodulation (InterStim®) therapy for refractory urgency urinary incontinence (UUI). The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment (ROSETTA) trial compares changes in urgency urinary incontinence episodes over 6 months, as well as other lower urinary tract symptoms, adverse ...[more]

PMID: 24486637

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Project description:PURPOSE:Sacral neuromodulation and intradetrusor onabotulinumtoxinA injection are therapies for refractory urgency urinary incontinence. Sacral neuromodulation involves surgical implantation of a device that can last 4 to 6 years while onabotulinumtoxinA therapy involves serial office injections. We assessed the cost-effectiveness of 2-stage implantation sacral neuromodulation vs 200 units onabotulinumtoxinA for the treatment of urgency urinary incontinence. MATERIALS AND METHODS:Prospective economic evaluation was performed concurrent with the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment) randomized trial of 386 women with 6 or more urgency urinary incontinence episodes on a 3-day diary. Analysis is from the health care system perspective with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs are in 2018 U.S. dollars. Effectiveness was measured in quality adjusted life-years (QALYs) and reductions in urgency urinary incontinence episodes per day. We generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS:Two-year costs were higher for sacral neuromodulation than for onabotulinumtoxinA ($35,680 [95% CI 33,920-37,440] vs $7,460 [95% CI 5,780-9,150], p <0.01), persisting through 5 years ($36,550 [95% CI 34,787-38,309] vs $12,020 [95% CI 10,330-13,700], p <0.01). At 2 years there were no differences in mean reduction in urgency urinary incontinence episodes per day (-3.00 [95% CI -3.38 - -2.62] vs -3.12 [95% CI -3.48 - -2.76], p=0.66) or QALYs (1.39 [95% CI 1.34-1.44] vs 1.41 [95% CI 1.36-1.45], p=0.60). The probability that sacral neuromodulation is cost-effective relative to onabotulinumtoxinA is less than 0.025 for all willingness to pay values below $580,000 per QALY at 2 years and $204,000 per QALY at 5 years. CONCLUSIONS:Although both treatments were effective, the high cost of sacral neuromodulation is not good value for treating urgency urinary incontinence compared to 200 units onabotulinumtoxinA.

Project description:ImportanceWomen with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information.ObjectiveTo assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence.Design, setting, and participantsMulticenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence.InterventionsCystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189).Main outcomes and measuresPrimary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events.ResultsOf the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse effects (88.4 vs 85.1; mean difference, 3.3; 95% CI, -1.9 to 8.5; P = .22), and treatment preference (92.% vs 89%; risk difference, -3%; 95% CI, -16% to 10%; P = .49). Urinary tract infections were more frequent in the onabotulinumtoxinA group (35% vs 11%; risk difference, -23%; 95% CI, -33% to -13%; P < .001). The need for self-catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group. Neuromodulation device revisions and removals occurred in 3%.Conclusions and relevanceAmong women with refractory urgency urinary incontinence, treatment with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance. In addition, it resulted in a higher risk of urinary tract infections and need for transient self-catheterizations.

Project description:PurposeWe systematically reviewed preclinical and clinical studies on bladder chemodenervation with onabotulinumtoxin A to highlight current limitations and future drug delivery approaches.Materials and methodsWe identified peer reviewed basic and clinical research studies of onabotulinumtoxin A in the treatment of neurogenic bladder and refractory idiopathic overactive bladder published between March 2000 and March 2016. Paired investigators independently screened 125 English language articles to identify controlled studies on onabotulinumtoxin A administration in the MEDLINE® database and abstracts presented at annual American Urological Association meetings. The review yielded an evidence base of more than 50 articles relevant to the approach of injection-free onabotulinumtoxin A chemodenervation.ResultsThe efficacy and safety of intradetrusor injection of onabotulinumtoxin A for the treatment of overactive bladder are sensitive to injection volume and depth, and this issue has motivated researchers to study injection-free modes of drug delivery into the bladder. Urothelial denudation with protamine sulfate or dimethyl sulfoxide, liposome encapsulated onabotulinumtoxin A and other physical approaches are being studied to increase toxin permeability and avoid intradetrusor injections. Liposome encapsulated onabotulinumtoxin A enhances toxin activity while reducing its toxin degradation. The safety and efficacy of liposome encapsulated onabotulinumtoxin A were tested in a multicenter, placebo controlled study. Although this treatment successfully reduced urinary frequency and urgency, it did not significantly reduce urgency urinary incontinence episodes.ConclusionsIntradetrusor injection of onabotulinumtoxin A is a safe and effective treatment as reported in several large multicenter, randomized controlled trials. Injection of the toxin into the bladder wall impairs afferent and efferent nerves, but injection-free drug delivery approaches only impair the bladder afferent nerves. Further studies are needed to develop better drug delivery platforms that overcome the drawbacks of intradetrusor injection, increase patient acceptance and reduce treatment costs.

Dataset Information

The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment: ROSETTA trial.

Publications

The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment: ROSETTA trial.

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