Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment (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®.
Refractory Urge Urinary Incontinence
Device: InterStim® device
Drug: Botox® injection
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: InterStim® therapy||
Device: InterStim® device
Subjects will be screened to assess eligibility criteria and baseline number of daily urge urinary incontinence episodes. Candidates will be approached for enrollment and will be consented and enrolled into the study. A minimum of a 3-week washout period is required for any subject currently on anticholinergic therapy prior to randomization. Eligible subjects will complete baseline assessments, be randomized and scheduled for either a first stage lead placement (FSLP) InterStim® or Botox A® injection visit. 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||
Drug: Botox® injection
Subjects will be screened to assess eligibility criteria and baseline number of daily urge urinary incontinence episodes. Candidates will be approached for enrollment and consented and enrolled into the study. A minimum of a 3-week washout period is required for any subject currently on anticholinergic therapy prior to randomization. Eligible subjects will complete baseline assessments, be randomized and scheduled for either a first stage lead placement (FSLP) InterStim® or 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.
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).
|Contact: Cindy Amundsen, MDfirstname.lastname@example.org|
|Contact: Dennis Wallace, PhDemail@example.com|
|United States, Alabama|
|University of Alabama at Birmingham, Department of Obstetrics and Gynecology||Recruiting|
|Birmingham, Alabama, United States, 35249-7333|
|Contact: Velria Willis, RN, BSN 205-975-8522 firstname.lastname@example.org|
|Principal Investigator: Holly Richter, PhD, Md|
|United States, California|
|University of California, San Diego, Women's Pelvic Medicine Center||Recruiting|
|La Jolla, California, United States, 92037|
|Contact: JoAnn Columbo 858-657-6827 email@example.com|
|Principal Investigator: Shawn Menefee, MD|
|United States, New Mexico|
|University of New Mexico Health Sciences Center||Recruiting|
|Albuquerque, New Mexico, United States, 87131-0001|
|Contact: Anne Fullilove 505-272-6391 AMFullilove@salud.unm.edu|
|Principal Investigator: Yuko Kumesu, MD|
|United States, North Carolina|
|Duke Division of Urogynecology and Reconstructive Pelvic Surgery||Recruiting|
|Durham, North Carolina, United States, 277707|
|Contact: Mary Raynor, RN, BSN 919-401-1016 firstname.lastname@example.org|
|Principal Investigator: Cindy Amundsen, MD|
|United States, Ohio|
|Cleveland Clinic, Obstretric and Gynecology and Women Health Institute||Recruiting|
|Cleveland, Ohio, United States, 44194|
|Contact: Ly Pung, RN, BSN 216-445-2494 email@example.com|
|Principal Investigator: Sandip Vasavada, MD|
|United States, Oregon|
|Oregon Health and Science University, Kohler Pavilion||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: W. Thomas Gregory, MD 503-418-4500|
|Principal Investigator: W. Thomas Gregory, MD|
|United States, Pennsylvania|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Michelle Kinglee 215-615-6569 firstname.lastname@example.org|
|Principal Investigator: Lily Arya, MD|
|Univesity of Pittsburgh, Magee-Womens Hospital||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Judy Gruss, RN 412-641-5388 email@example.com|
|Principal Investigator: Jerry Lowder, MD|
|United States, Rhode Island|
|Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery||Recruiting|
|Providence, Rhode Island, United States, 02903|
|Contact: Ann Meers, RN, CCRC 401-453-7560 firstname.lastname@example.org|
|Principal Investigator: Deborah L. Meyers, MD|
|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)|