Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment (ROSETTA)

This study is currently recruiting participants.
Verified April 2014 by NICHD Pelvic Floor Disorders Network
Sponsor:
Collaborators:
Duke University
University of Alabama at Birmingham
University of California, San Diego
The Cleveland Clinic
Brown University
University of New Mexico
University of Pennsylvania
University of Pittsburgh
Oregon Health and Science University
RTI International
Information provided by (Responsible Party):
dwallace, RTI International
ClinicalTrials.gov Identifier:
NCT01502956
First received: December 27, 2011
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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®.


Condition Intervention Phase
Refractory Urge Urinary Incontinence
Device: InterStim® device
Drug: Botox® injection
Phase 3

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by NICHD Pelvic Floor Disorders Network:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 380
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)
Arms Assigned Interventions
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.

Detailed Description:

Primary Aim:

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®).

Secondary Aims:

  • 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).
  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Non-pregnant adult female at least 21 years old, with no plans to become pregnant during the course of the trial) and if of child-bearing potential, with a negative pregnancy test, and if sexually active, must be using medically acceptable contraception.
  • 6 urge urinary incontinence episodes on a 3-day baseline bladder diary, with these urge incontinence episodes representing greater than 50% of the total incontinent episodes recorded.
  • Willing and able to complete all study related items and interviews.
  • Refractory urinary urge urinary incontinence: defined as (1) Persistent symptoms despite at least one or more conservative treatments (e.g. supervised behavioral therapy, supervised physical therapy); and (2)Persistent symptoms despite the use of a minimum of two anticholinergics, or unable to tolerate medication due to side effects, or has a contraindication to taking anticholinergic medication.
  • Currently not on an anticholinergic or antimuscarinic medication (e.g. oxybutynin, tolterodine, and/or fesoterodine) or be willing to stop medication for 3 weeks prior to completing baseline bladder diary and expected to remain off medications through duration of study.
  • Demonstrates ability (or have caregiver demonstrate ability) to perform clean intermittent self-catheterization.
  • Grossly neurologically normal on exam and no gross systemic neurologic conditions believed to affect urinary function.
  • Urodynamic assessment within the previous 18 months prior to enrollment or done after enrollment, prior to randomization.

Exclusion Criteria:

  • Neurologic diseases such as multiple sclerosis, Parkinson Disease, CVA within 6 months prior to enrollment, myasthenia gravis, Charcot-Marie-Tooth disease, clinically significant peripheral neuropathy, and complete spinal cord injury.
  • Untreated urinary tract infection (UTI).
  • Any prior use of either study therapy for treatment of urinary urge incontinence (Botox A® or Interstim®).
  • Current participation in any other conflicting interventional research study.
  • PVR >150 ml on 2 occasions within 6 months prior to enrollment (If the PVR value was obtained by ultrasound and was ≥150 ml, the PVR will be confirmed by catheterization which will be the gold standard)
  • Subjects with knowledge of planned MRIs or diathermy, except those allowable per Medtronic guidelines.
  • Current or prior bladder malignancy.
  • Surgically altered detrusor muscle, such as augmentation cystoplasty.
  • Subjects taking aminoglycosides.
  • Currently pregnant or lactating.
  • Subjects who are on ambulatory anticoagulant therapy, including aspirin, who are unable to discontinue treatment for 24 hours prior to bladder injection and staged InterStim® procedure.
  • Serum creatinine level greater than twice the upper limit of normal within the previous year prior to enrollment.
  • Surgical treatment for stress incontinence (sling, Burch or urethral injection) or pelvic organ prolapse recommended or planned at enrollment by study investigator(s).
  • Prior stress incontinence or prolapsed surgery within the last 6 months prior to enrollment.
  • Allergy to lidocaine or bupivacaine.
  • Prior pelvic radiation.
  • Uninvestigated hematuria.
  • Greater than or equal to Stage III vaginal prolapse.
  • Known allergy to Botox A®.
  • Use of a vaginal pessary.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01502956

Contacts
Contact: Cindy Amundsen, MD 919-401-1006 amund002@mc.duke.edu
Contact: Dennis Wallace, PhD 919-541-6271 dwallace@rti.org

Locations
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    vwillis@uabmc.edu   
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    jcolumbo@ucsd.edu   
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    mary.raynor@duke.edu   
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    pungl@ccf.org   
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    kingleem@uphs.upenn.edu   
Principal Investigator: Lily Arya, MD         
Univesity of Pittsburgh, Magee-Womens Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Judy Gruss, RN    412-641-5388    grusja@mail.magee.edu   
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    ameers@wihri.org   
Principal Investigator: Deborah L. Meyers, MD         
Sponsors and Collaborators
NICHD Pelvic Floor Disorders Network
Duke University
University of Alabama at Birmingham
University of California, San Diego
The Cleveland Clinic
Brown University
University of New Mexico
University of Pennsylvania
University of Pittsburgh
Oregon Health and Science University
RTI International
Investigators
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)
  More Information

Additional Information:
No publications provided

Responsible Party: dwallace, Project Director, RTI International
ClinicalTrials.gov Identifier: NCT01502956     History of Changes
Other Study ID Numbers: PFDN 20
Study First Received: December 27, 2011
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by NICHD Pelvic Floor Disorders Network:
Refactory Urinary Urge Incontinence
Botox A®
Interstim® Device

Additional relevant MeSH terms:
Urinary Incontinence
Urinary Incontinence, Urge
Urinary Bladder, Overactive
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Urinary Bladder Diseases
Botulinum Toxins
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014