Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment (ROSETTA) (ROSETTA)
The purpose of this randomized, open-label, active-control trial is to compare the effectiveness of intra-detrusor botulinum toxin A (Botox A®, Allergan) versus sacral neuromodulation (InterStim®, Medtronic) for the treatment of refractory urge urinary incontinence. In addition, the study will evaluate select technical attributes of the interventions as well as the effect of these two interventions on other lower urinary tract and pelvic floor symptoms.
Hypothesis: InterStim® therapy will result in a greater reduction in daily urge urinary incontinence episodes over the 6-month follow-up period as compared to Botox A® injection.
A supplemental study investigates whether biological markers including those related to inflammation and connective tissue remodeling change following treatments with Botox A® and Interstim®.
|Urinary Incontinence, Urge||Device: InterStim® device Drug: Botox® injection||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment (ROSETTA)|
- Number of urge urinary incontinence episodes (UUIE) [ Time Frame: Baseline to 6-month visit ]The primary outcome is the change from baseline in mean number of UUIE over the first 6 month visit period (1, 2, 3 4, 5 and 6 month assessments); and is measured using 3-day bladder diaries administered monthly for the first 6 month visit period.
- Improvement of Bladder Function [ Time Frame: 6, 12, and 24 month visits ]Proportion of subjects who report adequate improvement of their bladder function with the Patient Global Impression of Improvement Questionnaire (PGI-I) at 6, 12, and 24 month visits.
- Change in Overactive Bladder [ Time Frame: 6, 12, and 24 month visits ]Change from baseline to 6, 12 and 24 month visits in the Overactive Bladder Questionnaire Short Form (OABq-SF).
- Urinary Frequency and Nocturia [ Time Frame: 6, 12, and 24 month visits ]Change from baseline to 6, 12 and 24 month visits in urinary frequency and nocturia as measured by the 3 day bladder diary and severity of urge incontinence symptoms as measured by the Sandvik questionnaire.
- Treatment Satisfaction [ Time Frame: 6, 12, and 24 month visits ]The proportion of subjects satisfied with their treatment as measured by the Overactive Bladder Satisfaction of Treatment questionnaire (OAB-SATq) at 6, 12 and 24 month visits.
- Quality of Life [ Time Frame: 6, 12, and 24 month visits ]Changes from baseline to 6, 12 and 24 month visits in quality of life measures as measured by the Urinary Distress Inventory Short Form (UDI-SF), Incontinence Impact Questionnaire Short Form (IIQ-SF), Pelvic Organ Prolapse/Urinary Incontinence/Sexual Function Questionnaire Short Form (PISQ-SF), St Mark's (Vaizey) questionnaire for bowel incontinence, and the Health Utilities Index Mark 3 (HUI-3).
- Cost of Therapies [ Time Frame: Up to 24 months or before if subject does not complete study ]The cost of InterStim® therapy and Botox A® therapy as determined by utilization of medical resources for cost-effectiveness analysis.
- Safety and Burden of Therapies [ Time Frame: Up to 24 months or before if subject does not complete study ]Occurrence of adverse events for InterStim® of infection, pain, decreased efficacy, need for surgical revision and for Botox A® of need for CISC or UTI; proportion of subjects with voiding dysfunction/partial urinary retention requiring catheterization (PVR>300 ml or PVR > 200 ml and symptoms of incomplete voiding); proportion of subjects with Botox A® reinjection or reprogramming of InterStim® device; and proportion of subjects with infection, pain or lead migration of the Interstim® device recorded during follow-up visits.
|Study Start Date:||February 2012|
|Study Completion Date:||July 2016|
|Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Active Comparator: InterStim® device
The FSLP InterStim® device is to be done within 3 months of enrolling/consenting. The 1st stage is lead placement into the S3 foramen with best response to stimulation. The 4 electrodes will be tested and set to an amplitude that achieves comfortable stimulation in the vaginal, perineal, or rectal sensation. If =/>50% improvement, participant will then have the 2nd stage IPG implantation, 8-18 days after last FSLP. If there is a technical problem with lead on 1st FSLP, then the participant can have a 2nd FSLP and may go on to have IPG implantation with lead replacement. The 2nd FSLP must be initiated no longer than 1 month since the initiation of the 1st FSLP. If the participant is a non-responder and there is no technical problem, then the lead is removed.
Device: InterStim® device
Eligible subjects will complete baseline assessments, be randomized and scheduled for first stage lead placement (FSLP) InterStim®. The criterion for an initial clinical response to InterStim® therapy will be defined as a ≥50% improvement in the mean number of UUIE/day on a minimum 3 day bladder diary, completed during the 7-14 days following the first stage lead placement (FSLP). Subjects with a ≥ 50% improvement mean number of UUIE/day will be eligible to proceed with implantation of the implantable pulse generator (IPG). Subjects will then be followed monthly to determine the response to therapy.
Active Comparator: Botox® injection
Total of 200 units of Botox A will be dissolved into 10mL of saline and injected into the bladder within 3 months of enrolling/consenting. Participants determined to have a clinical response at the 1 month visit (post 1st injection) may receive additional injections between 6-24 months.
Drug: Botox® injection
Eligible subjects will complete baseline assessments, be randomized and scheduled for Botox A® injection visit. Subjects who received a Botox A® injection will be assessed for a clinical response, at 1 month from injection, using the same clinical criterion (≥50% improvement in the mean number of UUIE/day on a 3 day bladder diary completed prior to the 1 month visit). Those subjects that experience a clinical response, at one month, will be eligible for a repeat Botox A® injection after 6 months, if they experience degradation of clinical effect, using the PGSC.
Other Name: Botox
To compare the change from baseline in the number of urge urinary incontinence episodes (UUIE) over 6 the six month follow-up period in women randomized to sacral neuromodulation (InterStim®) therapy, versus those randomized to intra-detrusor injection with 200 units of botulinum toxin A (Botox A®).
- Long Term Efficacy: To compare the long-term (12 and 24 month) efficacy outcomes in women randomized to sacral neuromodulation(InterStim®) therapy, versus those randomized to intra-detrusor injection with 200 units of botulinum toxin A (Botox A®). Secondary efficacy outcomes, collected at 12 and 24 months as well as 6 months,include adequate control of their urge urinary incontinence, change in bothersome symptoms of urinary urge incontinence (UUI), severity of urge incontinence, urinary frequency, nocturia, subject satisfaction with therapy, quality of life measures and bowel and sexual function.
- Cost Effectiveness: To compare utilization of medical resources for cost effectiveness analysis and cost-utility between treatment groups.
- Treatment Safety and Burden: To assess safety profile and treatment burden of both interventions by comparing adverse event incidence between treatment arms, and also by obtaining estimates of incidence of treatment-specific safety and burden outcomes. Safety and burden outcomes for Botox A® injections include receipt of additional injections and intermittent catheterization due to voiding dysfunction/partial urinary retention. Safety and burden outcomes for InterStim® device include infection, pain, lead migration, reprogramming (and reasons for) and surgical revision (and reasons for).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01502956
|United States, Alabama|
|University of Alabama at Birmingham, Department of Obstetrics and Gynecology|
|Birmingham, Alabama, United States, 35249-7333|
|United States, California|
|University of California, San Diego, Women's Pelvic Medicine Center|
|La Jolla, California, United States, 92037|
|United States, New Mexico|
|University of New Mexico Health Sciences Center|
|Albuquerque, New Mexico, United States, 87131-0001|
|United States, North Carolina|
|Duke Division of Urogynecology and Reconstructive Pelvic Surgery|
|Durham, North Carolina, United States, 277707|
|United States, Ohio|
|Cleveland Clinic, Obstretric and Gynecology and Women Health Institute|
|Cleveland, Ohio, United States, 44194|
|United States, Oregon|
|Oregon Health and Science University, Kohler Pavilion|
|Portland, Oregon, United States, 97239|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Univesity of Pittsburgh, Magee-Womens Hospital|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Rhode Island|
|Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery|
|Providence, Rhode Island, United States, 02903|
|Study Chair:||Cindy Amundsen, MD||Duke University|
|Principal Investigator:||Holly Richter, PhD, MD||University of Alabama at Birmingham|
|Principal Investigator:||Shawn A. Menefee, MD||Kaiser Permanente, San Diego, CA|
|Principal Investigator:||Sandip Vasada, MD||The Cleveland Clinic|
|Principal Investigator:||Deborah L. Myers, MD||Brown/Women and Infants Hospital of Rhode Island|
|Principal Investigator:||Yoko Kumesu, MD||University of New Mexico|
|Principal Investigator:||Lily Arya, MD||University of Pennsylvania|
|Principal Investigator:||Jerry Lowder, MD||University of Pittsburgh|
|Principal Investigator:||W. Thomas Gregory, MD||Oregon Health and Science University|
|Principal Investigator:||Dennis Wallace, PhD||RTI International|
|Principal Investigator:||Susan Meikle, MD, MSPH||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|