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

• ClinicalTrials.gov Identifier: NCT01090739
• Recruitment Status: Completed
• First Posted: March 22, 2010
• Results First Posted: August 26, 2016
• Last Update Posted: August 26, 2016
• Sponsor: ASTORA Women's Health
• Information provided by (Responsible Party): ASTORA Women's Health

Tracking Information

• First Submitted Date: March 19, 2010
• First Posted Date: March 22, 2010
• Results First Submitted Date: April 19, 2016
• Results First Posted Date: August 26, 2016
• Last Update Posted Date: August 26, 2016
• Study Start Date: April 2010
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 25, 2016)

Percentage of Responders [ Time Frame: 12 Months ]

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.

Original Primary Outcome Measures (submitted: March 19, 2010)

Efficacy [ Time Frame: 12 Months ]

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 success.

Current Secondary Outcome Measures (submitted: August 25, 2016)

• Change in Fecal Incontinence Episodes [ Time Frame: 36 Month Follow-up Visit ]
  Number of fecal incontinence episodes in a 14 day period
• Change in Fecal Incontinence Days [ Time Frame: 36 Month Follow-up Visit ]
  Number of fecal incontinence days in a 14 day period
• Change in Urge Fecal Incontinence Episodes [ Time Frame: 36 Month Follow-up Visit ]
  Number of urge fecal incontinence episodes in a 14 day period
• Change in Wexner Symptom Severity Score [ Time Frame: 36 Month Follow-up Visit ]
  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.
• Change in Fecal Incontinence Quality of Life Score [ Time Frame: 36 Month Follow-up Visit ]
  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.
• Change in Pelvic Floor Distress Inventory (PFDI-20) Scores [ Time Frame: 36 Month Follow-up Visit ]
  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.
• Change in Pelvic Floor Impact Questionnaire (PFIQ-7) Scores [ Time Frame: 36 Month Follow-up Visit ]
  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.
• Change in Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) [ Time Frame: 36 Month Follow-up Visit ]
  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.
• Change in Numeric Pelvic Pain Scale (NPPS) [ Time Frame: 12 Month Follow-up Visit ]
  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.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: August 25, 2016)

• Change in the Haff Surgical Satisfaction Questionnaire (SSQ-8) [ Time Frame: 36 Month Follow-up Visit ]
  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
• Change in Health Resource Usage: # Pads Per Day Subject Took for FI [ Time Frame: 36 Month Follow-up Visit ]
  Change in health resource usage using sponsor-created questionnaire: # days in hospital due to FI
• Change in Health Resource Usage: # Days in Hospital, Took Off Work, or Others Took Off Work Due to FI [ Time Frame: 36 Month Follow-up Visit ]
  Change in health resource usage using sponsor-created questionnaire
• Change in Health Resource Usage: # Physician Visits Due to FI [ Time Frame: 36 Month Follow-up Visit ]
  Change in health resource usage using sponsor-created questionnaire

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Study to Investigate the Effectiveness of the TOPAS System to Treat Fecal Incontinence
• Official Title: An Investigation of the Treatment of Fecal Incontinence Using the TOPAS Sling System For Women (TRANSFORM)
• Brief Summary: 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.

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
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Fecal Incontinence

Intervention

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.

Study Arms

Experimental: TOPAS

TOPAS Treatment for Fecal Incontinence

Intervention: Device: TOPAS Treatment for Fecal Incontinence

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 25, 2016): 207
• Original Estimated Enrollment (submitted: March 19, 2010): 152
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01090739
• Other Study ID Numbers: WC0807
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Each site was provided with their individual participant data

• Responsible Party: ASTORA Women's Health
• Study Sponsor: ASTORA Women's Health
• Collaborators: Not Provided

Investigators

• Study Chair: Anders Mellgren, MD, PhD; University of Illinois at Chicago
• Study Chair: Dee Fenner, MD; University of Michigan

• PRS Account: ASTORA Women's Health
• Verification Date: August 2016