Clinical Study to Investigate the Effectiveness of the TOPAS System to Treat Fecal Incontinence (TRANSFORM)

An Investigation of the Treatment of Fecal Incontinence Using the TOPAS Sling System For Women (TRANSFORM)

The purpose of this study is to demonstrate that the TOPAS System effectively treats fecal incontinence in women as measured by a 50% reduction in the number of FI episodes in a 14 day bowel diary at 12 months.

Study Overview

• Status: Completed
• Conditions: Fecal Incontinence
• Intervention / Treatment: Device: TOPAS Treatment for Fecal Incontinence

Detailed Description

This is a prospective, multi-center, single-arm, open-label, two- stage, adaptive study conducted to obtain data to demonstrate the safety and effectiveness of the TOPAS system for the treatment of FI in women who have failed conservative therapy. It was approved by the FDA for up to 152 implanted subjects at up to 15 investigational sites in the US. Eight study centers are led by a Colorectal Surgeon and seven centers are led by an Urogynecologist.

This study is being conducted in compliance with Title 21 CFR Parts 11, 50, 54, 56, and 812; the principles of GCP as set forth in the World Medical Association Declaration of Helsinki (2008); and the ISO standard 14155:2011 (Clinical investigation of medical devices for human subjects - Good clinical practice).

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California SF - Mt Zion Medical Center
  • Florida
    • Tampa, Florida, United States, 33605
      • University of South Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Foundation - Florida
  • Georgia
    • Toccoa, Georgia, United States, 30577
      • Raybon OB-GYN
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina - Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation - Ohio
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 76104
      • University of Oklahoma
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • St. Luke's Hospital
  • Texas
    • Houston, Texas, United States, 77054
      • Womens Hospital of Texas
  • Washington
    • Spokane, Washington, United States, 99204
      • Sacred Heart Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Subject is/has:

1. An adult (>/= 18 years) female.
2. FI symptoms for a minimum of 6 months.
3. Failed two modalities of conservative therapies such as Dietary Modification, Pharmacologic Intervention, or Pelvic Floor Muscle Training.
4. <50 years old OR if >/= 50 years old, has had a negative cancer screening examination of the colon according screening guidelines (colonoscopy or barium enema + flexible sigmoidoscopy) within the past 3 years prior to informed consent date. (Note: if not done, the investigating physician must provide written justification for not having this exam and must be following the American Cancer Society Guidelines).
5. FI episodes ≥ 4 in 14 day period.

Exclusion Criteria:

Subject is/has

1. Unable or unwilling to sign Informed Consent Form or comply with study requirements.
2. Currently enrolled in or plans to enroll in any concurrent drug and/or device study that may confound the results of this study as determined by AMS.
3. Allergic to polypropylene.
4. Pregnant or planning a future pregnancy.
5. Less than 12 months (365 days) postpartum.
6. Pelvic prolapse >/=1 cm beyond the hymen (Stage III & IV)
7. Had stress urinary incontinence (SUI) or anterior repair within 3 months (90 days) prior to TOPAS Sling System implantation.
8. Had a hysterectomy, Sphincteroplasty, or Posterior surgery within 6 months (180 days) prior to TOPAS Sling System implantation.
9. Had rectal surgery (such as rectopexy) within 12 months (365 days) of TOPAS Sling System implantation.
10. Planning pelvic surgery within 12 months (365 days) post implant
11. Current Grade III or IV hemorrhoids.
12. Neurological or psychological condition as cause of FI such as MS, dementia, brain tumor.
13. Diagnosed Inflammatory Bowel Disease (for example, ulcerative colitis or Crohn's disease).
14. Chronic, watery diarrhea, unmanageable by drugs or diet, as primary cause of fecal incontinence.
15. Severe chronic constipation, including obstructive defecatory disorder.
16. External full thickness rectal prolapse.
17. A history of laxative abuse within the past 5 years.
18. Had previous rectal resection.
19. Active pelvic infection, perianal or recto-vaginal fistula.
20. Congenital anorectal malformations or chronic 4th degree lacerations and cloacae.
21. History of therapeutic radiation for cancers of the pelvis.
22. Currently implanted with a sacral nerve stimulator.
23. Contraindicated for surgery or having any condition that would compromise wound healing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TOPAS; TOPAS Treatment for Fecal Incontinence	Device: TOPAS Treatment for Fecal Incontinence; The TOPAS Treatment for Fecal Incontinence is implanted using a minimally invasive trans-obturator approach; two needle passers deliver the sling assembly. Two small posterior incisions facilitate the post-anal placement of the mesh.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders	The primary endpoint for efficacy is the 14 day bowel diary documenting liquid or solid fecal incontinence episodes. A 50% reduction in the number of FI episodes is considered a treatment responder.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fecal Incontinence Episodes	Number of fecal incontinence episodes in a 14 day period	36 Month Follow-up Visit
Change in Fecal Incontinence Days	Number of fecal incontinence days in a 14 day period	36 Month Follow-up Visit
Change in Urge Fecal Incontinence Episodes	Number of urge fecal incontinence episodes in a 14 day period	36 Month Follow-up Visit
Change in Wexner Symptom Severity Score	Wexner Symptom Severity Score for fecal incontinence (also known as the Cleveland Clinic Incontinence Score) as described by Jorge and Wexner, 1993 (Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum. 1993 Jan;36(1):77-97). Measured on a 0-20 scale with lower scores equal to less fecal incontinence.	36 Month Follow-up Visit
Change in Fecal Incontinence Quality of Life Score	Fecal Incontinence Quality of Life Score as described by Rockwood et al., 2000 (Rockwood TH, Church JM, Fleshman JW, Kane RL, Mavrantonis C, Thorson AG, Wexner SD, Bliss D, Lowry AC. Fecal Incontinence Quality of Life Scale: quality of life instrument for patients with fecal incontinence. Dis Colon Rectum. 2000 Jan;43(1):9-16; discussion 16-7). Four domains of lifestyle, coping, depression, and embarrassment. Measured on a 0-4 scale with higher scores equal to better quality of life.	36 Month Follow-up Visit
Change in Pelvic Floor Distress Inventory (PFDI-20) Scores	Short-form version of the Pelvic Floor Distress Inventory (PFDI-20) as described by Barber et al., 2005 (Barber MD, Walters MD, Bump RC. Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7. Am J Obstet Gynecol. 2005 Jul;193(1):103-13). The short-form version of the Pelvic Floor Distress Inventory has a total of 20 questions and 3 scales (Urinary Distress Inventory, Pelvic Organ Prolapse Distress Inventory, and Colorectal-Anal Distress Inventory). Total PFDI score measured on a 0-300 scale with higher scores equal to greater pelvic floor distress. As with the Total PFDI Score, higher subscale scores equal greater pelvic floor distress, on a 0-100 scale.	36 Month Follow-up Visit
Change in Pelvic Floor Impact Questionnaire (PFIQ-7) Scores	Short-form version of the Pelvic Floor Impact Questionnaire (PFIQ-7) as described by Barber et al., 2005 (Barber MD, Walters MD, Bump RC. Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7. Am J Obstet Gynecol. 2005 Jul;193(1):103-13). The short-form version of the Pelvic Floor Impact Questionnaire has a total of 7 questions and 3 scales (Urinary Impact, Pelvic Organ Prolapse Impact, and Colorectal-Anal Impact). Total PFIQ score measured on a 0-300 scale with higher scores equal to greater pelvic floor impact. Subscales scored on 0-100 scale and the higher the score the greater pelvic floor impact, exactly like the Total PFIQ score.	36 Month Follow-up Visit
Change in Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12)	Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) as described by Rogers RG, Coates KW, Kammerer-Doak D, Khalsa S, Qualls C. A short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Int Urogynecol J Pelvic Floor Dysfunct. 2003 Aug;14(3):164-8; discussion 168. Measured on a 0-48 scale with higher scores equal to better sexual function.	36 Month Follow-up Visit
Change in Numeric Pelvic Pain Scale (NPPS)	Numeric Pelvic Pain Scale (NPPS) adapted from McCafferty M, Pasero C. Pain: Clinical Manual. 2nd ed. Philadelphia: Mosby Inc.; 1999. Chapter 3, Assessment Tools; p. 58-75. The NPPS is scored on a 0-10 scale with higher scores indicating more severe pain. Since the NPPS was introduced later in the study, earlier implanted subjects did not have the baseline NPPS score and a change from baseline could not be calculated.	12 Month Follow-up Visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Haff Surgical Satisfaction Questionnaire (SSQ-8)	The SSQ-8 is an 8 item questionnaire to assess subject surgical satisfaction as described by Murphy M, Sternschuss G, Haff R, van Raalte H, Saltz S, Lucente V. Quality of life and surgical satisfaction after vaginal reconstructive vs. obliterative surgery for the treatment of advanced pelvic organ prolapse. Am J Obstet Gynecol. 2008 May;198(5):573.e1-7. The SSQ-8 was collected as an optional one-time assessment from implanted subjects between the 3 and 36 month visits. Scale is scored on 0-100 with higher scores are better	36 Month Follow-up Visit
Change in Health Resource Usage: # Pads Per Day Subject Took for FI	Change in health resource usage using sponsor-created questionnaire: # days in hospital due to FI	36 Month Follow-up Visit
Change in Health Resource Usage: # Days in Hospital, Took Off Work, or Others Took Off Work Due to FI	Change in health resource usage using sponsor-created questionnaire	36 Month Follow-up Visit
Change in Health Resource Usage: # Physician Visits Due to FI	Change in health resource usage using sponsor-created questionnaire	36 Month Follow-up Visit

Collaborators and Investigators

• Sponsor: ASTORA Women's Health
• Investigators: Study Chair: Anders Mellgren, MD, PhD, University of Illinois at Chicago; Study Chair: Dee Fenner, MD, University of Michigan

Publications and helpful links

General Publications

• Mellgren A, Zutshi M, Lucente VR, Culligan P, Fenner DE; TOPAS Study Group. A posterior anal sling for fecal incontinence: results of a 152-patient prospective multicenter study. Am J Obstet Gynecol. 2016 Mar;214(3):349.e1-8. doi: 10.1016/j.ajog.2015.10.013. Epub 2015 Oct 19.

Helpful Links

• Primary (1 Year) Results Manuscript

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: March 19, 2010
• First Submitted That Met QC Criteria: March 19, 2010
• First Posted (Estimate): March 22, 2010

Study Record Updates

• Last Update Posted (Estimate): August 26, 2016
• Last Update Submitted That Met QC Criteria: August 25, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Women; Fecal incontinence; Accidental bowel leakage; Failure conservative therapy; Class III medical device; Surgical mesh
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Fecal Incontinence
• Other Study ID Numbers: WC0807

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Each site was provided with their individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No