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

NCT01502956 | Completed Phase 3 Results DMC

• 2 other identifiers: PFDN 20U01HD069031
• Study Type: interventional
• Target: 386
• Locations: 1 country
• Sites: 9

Brief Summary

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®.

Conditions

Urinary Incontinence, Urge

Keywords

Refractory Urinary Urge Incontinence; Botox A®; Interstim® Device

Outcome Measures

Primary Outcomes (1)

• Number of Urge Urinary Incontinence (UUI) Episodes

  The primary outcome is the change from baseline in mean number of UUI episodes 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.

  6 Months

Secondary Outcomes (9)

• Number of Participants With Improvement of Bladder Function and Urinary Leakage

  6 Months

• Change in Overactive Bladder

  6 Months

• Urinary Frequency and Nocturia

  6 Months

• Severity of Urge Incontinence Symptoms

  6 Months

• Treatment Satisfaction (OAB-SATq Treatment Satisfaction, Adverse Effects, Treatment Endorsement, and Convenience)

  6 months

Study Arms (2)

InterStim® device

ACTIVE COMPARATOR

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

Botox® injection

ACTIVE COMPARATOR

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

Interventions

InterStim® device 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.

InterStim® device

Botox® injection DRUG

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.

Also known as: Botox

Botox® injection

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• NICHD Pelvic Floor Disorders Network: lead
• Duke University: collaborator
• University of Alabama at Birmingham: collaborator
• University of California, San Diego: collaborator
• The Cleveland Clinic: collaborator
• Brown University: collaborator
• University of New Mexico: collaborator
• University of Pennsylvania: collaborator
• University of Pittsburgh: collaborator
• Oregon Health and Science University: collaborator
• RTI International: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (9)

University of Alabama at Birmingham, Department of Obstetrics and Gynecology

Birmingham, Alabama, 35249-7333, United States

Location

University of California, San Diego, Women's Pelvic Medicine Center

La Jolla, California, 92037, United States

Location

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131-0001, United States

Location

Duke Division of Urogynecology and Reconstructive Pelvic Surgery

Durham, North Carolina, 277707, United States

Location

Cleveland Clinic, Obstretric and Gynecology and Women Health Institute

Cleveland, Ohio, 44194, United States

Location

Oregon Health and Science University, Kohler Pavilion

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Univesity of Pittsburgh, Magee-Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery

Providence, Rhode Island, 02903, United States

Location

Related Publications (5)

• Hendrickson WK, Amundsen CL, Rahn DD, Meyer I, Bradley MS, Smith AL, Myers DL, Jelovsek JE, Lukacz ES. Comparison of 100 U With 200 U of Intradetrusor OnabotulinumToxinA for Nonneurogenic Urgency Incontinence. Female Pelvic Med Reconstr Surg. 2021 Mar 1;27(3):140-146. doi: 10.1097/SPV.0000000000001020.

  PMID: 33620895 DERIVED

• Richter HE, Jelovsek JE, Iyer P, Rogers RG, Meyer I, Newman DK, Bradley MS, Harm-Ernandes I, Dyer KY, Wohlrab K, Mazloomdoost D, Gantz MG; Eunice Kennedy Shriver NICHD Pelvic Floor Disorders Network and the National Institutes of Health Office of Research on Women's Health. Characteristics Associated With Clinically Important Treatment Responses in Women Undergoing Nonsurgical Therapy for Fecal Incontinence. Am J Gastroenterol. 2020 Jan;115(1):115-127. doi: 10.14309/ajg.0000000000000482.

  PMID: 31895722 DERIVED

• Andy UU, Amundsen CL, Honeycutt E, Markland AD, Dunivan G, Dyer KY, Korbly NB, Bradley M, Vasavada S, Mazloomdoost D, Thomas S; NICHD Pelvic Floor Disorders Network. Sacral neuromodulation versus onabotulinumtoxinA for refractory urgency urinary incontinence: impact on fecal incontinence symptoms and sexual function. Am J Obstet Gynecol. 2019 Nov;221(5):513.e1-513.e15. doi: 10.1016/j.ajog.2019.06.018. Epub 2019 Jun 15.

  PMID: 31211964 DERIVED

• Komesu YM, Amundsen CL, Richter HE, Erickson SW, Ackenbom MF, Andy UU, Sung VW, Albo M, Gregory WT, Paraiso MF, Wallace D; Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Refractory urgency urinary incontinence treatment in women: impact of age on outcomes and complications. Am J Obstet Gynecol. 2018 Jan;218(1):111.e1-111.e9. doi: 10.1016/j.ajog.2017.10.006. Epub 2017 Oct 12.

  PMID: 29031894 DERIVED

• Amundsen CL, Richter HE, Menefee S, Vasavada S, Rahn DD, Kenton K, Harvie HS, Wallace D, Meikle S. The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment: ROSETTA trial. Contemp Clin Trials. 2014 Mar;37(2):272-83. doi: 10.1016/j.cct.2014.01.009. Epub 2014 Jan 30.

  PMID: 24486637 DERIVED

MeSH Terms

Conditions

Urinary Incontinence, Urge

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Urinary Incontinence; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Marie Gantz
• Organization: RTI International

mgantz@rti.org

919-597-5110

Study Officials

• Cindy Amundsen, MD

  Duke University

  STUDY CHAIR

• 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)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2011
• First Posted: January 2, 2012
• Study Start: February 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 2, 2018
• Results First Posted: March 8, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)