Background
The transobturator posterior anal sling (TOPAS) system is a posterior anal sling that is a minimally invasive, self-fixating polypropylene mesh intended to treat fecal incontinence (FI) in women who have failed conservative therapy.
Objective
We are reporting 1-year outcome in a prospective, multicenter study under investigational device exemption, evaluating this new treatment modality.
Study Design
A total of 152 women were implanted with the TOPAS system at 14 centers in the United States. FI was assessed preoperatively and at the 12-month follow up with a 14-day bowel diary, Cleveland Clinic Incontinence Scores, and FI Quality of Life questionnaires. Treatment success was defined as reduction in number of FI episodes of ≥50% compared to baseline. Missing bowel diary data were considered treatment failures. The Wilcoxon signed rank test was used to compare changes observed at 12 months vs baseline.
Results
Mean age was 59.6 years old (SD 9.7). The mean duration of FI was 110 mo (range 8-712) months. Mean length of the implant procedure was 33.4 (SD 11.6) minutes. Mean EBL was 12.9 (SD 10.5) mL. Average follow-up was 24.9 months. At 12 months, 69.1% of patients met the criteria for treatment success, and 19% of subjects reported complete continence. FI episodes/wk decreased from a median of 9.0 (range 2-40) at baseline to 2.5 (range 0-40) ( P < .001). FI days decreased from a median of 5.0 (range 1.5-7) at baseline to 2.0 (range 0-7) ( P < .001) over a 7-day period. FI associated with urgency decreased from a median at baseline of 2.0 (range 0-26) to 0 (range 0-14.5) ( P < .001). The mean Cleveland Clinic Incontinence Scores decreased from 13.9 at baseline to 9.6 at 12 months ( P < .001). FI Quality of Life scores for all 4 domains improved significantly from baseline to 12 months ( P < .001). A total of 66 subjects experienced 104 procedure- and/or device-related adverse events (AEs). Most AEs were short in duration and 97% were managed without therapy or with nonsurgical interventions. No treatment-related deaths, erosions, extrusions, or device revisions were reported. The most common AE categories were pelvic pain (n = 47) and infection (n = 26). Those subjects experiencing pelvic pain had a mean pain score (0-10 scale, 0 = no pain) during the 12-month follow-up of 1.2 (SD 2.4).
Conclusion
The TOPAS system provides significant improvements in FI symptoms and quality of life with an acceptable AE profile and may therefore be a viable minimally invasive treatment option for FI in women.
Introduction
Fecal incontinence (FI) (also called “accidental bowel leakage”) is defined as the involuntary loss of solid or liquid stool that causes social or hygienic problems. According to systematic reviews, it is estimated that FI affects between 0.4-18% of the general population. FI increases with age, from 2% in younger patients to close to 20% in older populations. Estimates from large population studies indicate approximately 5-10% of all adult women in the United States have FI with at least monthly incontinent episodes. FI has socially devastating effects on patients including shame, embarrassment, depression, poor self-image, and social isolation.
The initial first-line therapy for FI is conservative management with dietary modification, pharmacologic intervention, and/or pelvic floor muscle training. Patients who fail conservative management may be offered a sphincter repair for a disrupted external anal sphincter, injection of bulking agents, sacral nerve stimulation, or possibly placement of an artificial bowel sphincter or percutaneous tibial nerve stimulation. Unfortunately, none of these techniques have become a panacea for the treatment of FI patients. Therefore, new treatment modalities for FI are needed.
The TOPAS treatment for FI system is a new surgical device for women with FI first described by Rosenblatt et al. The procedure is minimally invasive and uses a needle-based delivery system to place through a transobturator approach a self-fixating, polypropylene mesh tape posterior to the anal canal ( Figure 1 ). Although the exact mechanism of action is unknown at the present time, it most likely facilitates the normal closing mechanism by enhancing focal structural support. The aim of the present study was to assess the efficacy and safety of the TOPAS system in treating FI under the rigors of a Food and Drug Administration (FDA)-approved investigational protocol.
Materials and Methods
This was a prospective, multicenter, single-arm study to assess the efficacy and safety of the TOPAS system for the treatment of FI in women. A maximum of 225 patients were allowed to be enrolled (ie, defined as signing the study informed consent form) and a total of 152 patients were initially planned for TOPAS system implantation at 8 colorectal surgical and 7 urogynecology study centers in the United States. Each center could implant a maximum of 28 patients. Participating surgeons underwent training on cadavers and were proctored by more experienced colleagues during the first 2 implantations. An independent data and safety monitoring board reviewed trial progress and safety. The study protocol was approved by the FDA and the institutional review boards at all participating institutions. The trial was registered with Clinicaltrials.gov ( NCT01090739 ).
All patients had FI symptoms for at least 6 months and had failed at least 2 modalities of conservative therapies (dietary modification, pharmacologic intervention, or pelvic floor muscle training). Inclusion criteria included: female patients, ≥18 years of age, negative colon cancer screening if ≥50 years old, and ≥4 FI episodes in a 14-day period ( Table 1 ). Exclusion criteria included: pregnancy or planning a future pregnancy, stage III and IV pelvic prolapse, recent pelvic surgery, inflammatory bowel disease, diarrhea, external rectal prolapse, previous rectal resection, active pelvic infection, or sacral nerve stimulator ( Table 1 ). To characterize the population, all patients had within a year of implantation a baseline anal manometry and endoanal ultrasound performed per institutional protocol. Results were not used as inclusion or exclusion criteria.
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Surgical procedure and follow-up
All patients received perioperative prophylactic antibiotics. The study device consisted of a single piece of knitted, type I polypropylene, monofilament mesh that was placed using a transobturator approach. The mesh was placed via a tunnel created between 2 small buttock incisions and then passed lateral to the rectum and vagina, around the ischiopubic bone, and out through the obturator foramen on each side using a curved insertion needle. Tensioning of the mesh was completed by pulling both the mesh and sheath assembly arms upward together until gentle tension was palpable in the mid anal canal. The insertion sheaths were then removed and the mesh was automatically self-fixated to the tissues.
Study follow-up visits for implanted patients were scheduled at 14-28 days (safety assessment only), and at 3, 6, and 12 months.
Primary efficacy objective
The primary efficacy objective was to demonstrate that implantation with the TOPAS system resulted in treatment success in >50% of the study patients. Treatment success was defined as at least a 50% reduction in the number of FI episodes from baseline to 12 months postoperatively as measured with a 14-day bowel dairy (Responder 50 ).
A bowel diary was completed pretreatment and at each visit. It recorded the number of FI episodes during a consecutive 14-day period and included information about urgency, consistency, and amount. Patients with missing 12-month bowel diaries were considered treatment failures for the primary efficacy endpoint analysis. The total sum of episodes was calculated as the first 14 consecutive days of data from the diary. If <10 days were available, that data point was considered missing.
Secondary efficacy objectives and safety
Secondary efficacy objectives included the reduction in incontinent days and urge FI episodes as measured from the bowel diary, reduction in FI symptom severity as measured by the Cleveland Clinic Incontinence Score (CCIS), the improvement in quality of life as measured by the FI Quality of Life (FIQOL) questionnaire, the effect on pelvic pain as measured by a 0- to 10-point numeric pain score, and to record and summarize all adverse events (AEs).
All AEs for the TOPAS system were recorded. AEs were either volunteered spontaneously by the subject or discovered as a result of questioning or physical exam by the study center. All AEs reported by the study centers were reviewed and adjudicated by an AE adjudication committee.
Statistical analysis
Using a Responder 50 rate for sacral neuro modulation treatment reported by Tjandra et al at 61.7%, a fixed-sample-size design with a sample size of N = 152 would achieve 84.9% power to reject the null hypothesis. However, to account for the unknown Responder 50 rate, this study was designed to allow an interim reassessment of sample size by employing the 2-stage adaptive design of Bauer and Köhne. Stage I consisted of the first 80 patients implanted. The primary objective was considered met if the P value for the stage I was < .0087. When the stage I cohort reached 1-year follow-up, an interim analysis was performed. Subjects missing 12-month follow-up data for any reason were included as treatment failures. The primary objective of the study was met at the end of the stage I, with a P value of .0048 (1-sided exact binomial test). Based on the interim analysis, the DSMB recommended that no sample size adjustment to stage II was needed. The results of the interim analysis were not shared with the clinical team and study investigators.
This report presents the “nominal” data for the study results based on all implanted subjects, similar to a conventional study design, where the final sample size is assumed as fixed in advance. Changes from baseline were analyzed with the Wilcoxon signed rank test or repeated measures mixed models. With the exception of the primary endpoint (which used a 1-sided binomial test as described above), all other tests of significance were 2-sided, with P value < .05 considered statistically significant. Univariate logistic regression models was performed to examine the effect of the baseline covariates on treatment success.
Statistical analyses were performed with software (SAS, Version 9.2; SAS Institute Inc, Cary, NC).
Materials and Methods
This was a prospective, multicenter, single-arm study to assess the efficacy and safety of the TOPAS system for the treatment of FI in women. A maximum of 225 patients were allowed to be enrolled (ie, defined as signing the study informed consent form) and a total of 152 patients were initially planned for TOPAS system implantation at 8 colorectal surgical and 7 urogynecology study centers in the United States. Each center could implant a maximum of 28 patients. Participating surgeons underwent training on cadavers and were proctored by more experienced colleagues during the first 2 implantations. An independent data and safety monitoring board reviewed trial progress and safety. The study protocol was approved by the FDA and the institutional review boards at all participating institutions. The trial was registered with Clinicaltrials.gov ( NCT01090739 ).
All patients had FI symptoms for at least 6 months and had failed at least 2 modalities of conservative therapies (dietary modification, pharmacologic intervention, or pelvic floor muscle training). Inclusion criteria included: female patients, ≥18 years of age, negative colon cancer screening if ≥50 years old, and ≥4 FI episodes in a 14-day period ( Table 1 ). Exclusion criteria included: pregnancy or planning a future pregnancy, stage III and IV pelvic prolapse, recent pelvic surgery, inflammatory bowel disease, diarrhea, external rectal prolapse, previous rectal resection, active pelvic infection, or sacral nerve stimulator ( Table 1 ). To characterize the population, all patients had within a year of implantation a baseline anal manometry and endoanal ultrasound performed per institutional protocol. Results were not used as inclusion or exclusion criteria.
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