Xenform Postmarket Surveillance Study

Study Overview
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Brief Summary
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To compare transvaginal repair with a biologic graft to traditional native tissue repair in women surgically treated for anterior and/or apical pelvic organ prolapse.

Detailed Description
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The primary objective is to evaluate clinical effectiveness of transvaginal repair with Xenform against traditional native tissue repair in women surgically treated for anterior and/or apical pelvic organ prolapse. Secondary objectives are to evaluate Xenform-related complications and subject reported outcomes. The primary endpoint of the study is to achieve non-inferiority of transvaginal repair with Xenform over native tissue repair at 36 months as compared to baseline. Success will be based on a composite of objective and subjective measures. Additionally, a co-primary endpoint of the study is to achieve non-inferiority of transvaginal repair with Xenform to native tissue repair for safety by comparing rates of serious device or serious procedure related complications between baseline and the 36 month time point. The secondary endpoints of the study include assessments of complications and subject reported outcomes.

Official Title
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A Prospective, Non-Randomized, Parallel Cohort, Multi-Center Study of Xenform vs. Native Tissue for the Treatment of Women With Anterior/Apical Pelvic Organ Prolapse

Conditions
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Pelvic Organ Prolapse

Intervention / Treatment
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* Procedure: Prolapse Repair


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is female Subject is at least 18 years of age Subject has pelvic organ prolapse with the leading edge at or beyond the hymen. At or beyond the hymen is defined as POP-Q scores of Ba≥0 (for prolapse of the anterior compartment alone) or C≥0 (for prolapse of the apical compartment alone) or C≥-1/2 TVL and Ba≥0 (for a multi-compartment prolapse that includes the anterior and apical compartments). Subject reports a bothersome bulge they can see or feel per PFDI-20, question 3, response of 2 or higher (i.e., responses of somewhat, moderately, or quite a bit) Subject or subject's legally authorized representative is willing to provide written informed consent Subject is willing and able to comply with the follow-up regimen Exclusion Criteria: Subject is pregnant or intends to become pregnant during the study Subject has an active or chronic systemic infection including any gynecologic infection, untreated urinary tract infection (UTI) or tissue necrosis Subject has history of pelvic organ cancer (e.g. uterine, ovarian, bladder, colo-rectal or cervical) Subject has had prior or is currently undergoing radiation, laser therapy, or chemotherapy in the pelvic area Subject has taken systemic steroids (within the last month), or immunosuppressive or immunomodulatory treatment (within the last 3 months) Subject has systemic connective tissue disease (e.g. scleroderma, systemic lupus erythematosus (SLE), Marfan syndrome, Ehlers Danlos, collagenosis, polymyositis, polymyalgia rheumatica) Subject has chronic systemic pain that includes the pelvic area or chronic focal pain that involves the pelvis Subject has uncontrolled diabetes mellitus (DM) Subject has a known neurologic or medical condition affecting bladder function (e.g., multiple sclerosis, spinal cord injury or stroke with residual neurologic deficit) Subject is seeking obliterative vaginal surgery as treatment for pelvic organ prolapse (colpocleisis) Subject is not able to conform to the modified dorsal lithotomy position Subject is currently participating in or plans to participate in another device or drug study during this study Subject has a known sensitivity to any Xenform component Subject has had previous prolapse repair with mesh in the target compartment Subject is planning to undergo a concomitant prolapse repair with use of mesh in the non-target compartment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Xenform<br>Prolapse Repair with Xenform Soft Tissue Repair Matrix | Procedure: Prolapse Repair<br>* Transvaginal anterior/apical pelvic organ prolapse repair<br>* Other names: Apical;|
| Active Comparator: Control<br>Prolapse Repair with Native Tissue Only | Procedure: Prolapse Repair<br>* Transvaginal anterior/apical pelvic organ prolapse repair<br>* Other names: Apical;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Success at 36 Months | The primary endpoint of the study was to achieve non-inferiority of transvaginal repair with Xenform over NTR at 36 months as compared to baseline. Success was based on a composite of objective and subjective measures. Subjective success was achieved if the patient denied symptoms of vaginal bulging per Pelvic Floor Distress Inventory (PFDI-20) question 3, answering no or yes but Not at all bothersome (< 2). Anatomic success (in the operated compartment): Anterior segment: Leading edge of anterior prolapse was at or above the hymen or Pelvic Organ Prolapse Quantification System (POP-Q) point Ba ≤ 0. Apical segment: The vaginal apex did not descend more than one-half into the vaginal canal (i.e., POP-Q point C < -1/2 TVL) for multi-compartment prolapse or POP-Q point C ≤ 0 for single compartment apical prolapse. No retreatment for POP: no additional surgical treatment for POP in the segment(s) of the vagina treated at the index surgery or no pessary use | 36 Months | 
| Number of Participants With One or More Serious Device-related and/or Procedure-Related Adverse Events | Co-primary endpoint of the study was to achieve non-inferiority of transvaginal mesh repair with Xenform to NTR for safety by comparing rates of serious device-related or serious procedure-related complications between baseline and the 36-month time point. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Mesh Erosion | Incidence of Mesh Erosion at 36 months | 36 months | 
| Number of Participants With Mesh Exposure | Incidence of mesh exposure at 36 months | 36 Months | 
| Number of Participants With de Novo Dyspareunia | Incidence of de novo dyspareunia at 36 months | 36 months | 
| Subject Specific Outcomes Measured With the Pelvic Floor Impact Questionnaire (PFIQ-7)] | Improvement in subject specific outcomes at 36 months compared to baseline [quality of life (QOL) per the Pelvic Floor Impact Questionnaire (PFIQ-7)] The PFIQ-7 is composed of three separate but related assessments: the UIQ-7 addresses the impact of urinary incontinence symptoms, the CRAIQ-7 addresses the impact of colorectal-anal or bowel symptoms, and the POPIQ-7 addresses impact of vaginal and pelvic symptoms. For each question, the low score (0) corresponds to not at all and the high score (3) corresponds to quite a bit. The scores for the UIQ-7, CRAIQ-7 and POPIQ-7 are additive to yield the final PFIQ-7 score. The scale scores are then added together to get the total PFIQ-7 score, which ranges from 0-300. A lower score means there is a lesser effect on quality of life. Reported score is change from baseline at 36 months. | 36 months | 
| Subject Specific Outcomes Measured by the Pelvic Floor Symptoms Per the Pelvic Floor Distress Inventory (PFDI-20) | Improvement in subject specific outcomes at 36 months compared to baseline [pelvic floor symptoms per the Pelvic Floor Distress Inventory (PFDI-20)] The Pelvic Floor Distress Inventory-20 (PFDI-20) is complimentary to the PFIQ-7 and focuses on symptoms of distress in the same compartmentalized fashion as the PFIQ-7. Like the PFIQ-7, the PFDI-20 consists of three components: Urinary Distress Inventory (UDI; 6 questions), the Pelvic Organ Prolapse Distress Inventory (POPDI; 6 questions), and Colorectal-Anal Distress Inventory (CRADI; 8 questions). The scoring for the PFDI-20 is similar to the PFIQ-7 where each individual component score is summed. The total ranges from 0 to 300 with a higher score indicating a greater impact to QOL (i.e., distress symptoms are more noticeable) and a lower score indicating a lesser impact to QOL (i.e., distress symptoms are less noticeable). The reported result is change from baseline at 36 months. | 36 months | 
| Subject Specific Outcomes Measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) | Improvement in subject specific outcomes at 36 months compared to baseline [change in sexual functioning per the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12)] This is a self-administered questionnaire and the responses are graded on a five-point Likert scale ranging from 0 (always) to 4 (never). Values range from 0 to 48 and a higher score indicates better sexual function. The reported result is change from baseline at 36 months. | 36 months | 
| Subject Specific Outcomes: Pain Measured by the TOMUS Pain Scale | Improvement in subject specific outcomes at 36 months compared to baseline [pain per the TOMUS pain scale] The TOMUS Pain Score, a visual analog instrument with a scale of 0 (no pain sensation) to 10 (most intense pain sensation imaginable), was used to assess pain associated with surgery for pelvic organ prolapse in this study. There are seven (7) questions each with a maximum score of 10 and a possible score range of 0-70). The reported results are change from baseline at 36 months. | 36 months | 
| Subject Improvement Measured by the Patient Global Impression of Improvement for Prolapse (PGI-I) | Assessment of subject's level of improvement, measured by the Patient Global Impression of Improvement for Prolapse (PGI-I) The Patient Global Impression of Improvement (PGI-I) for prolapse symptoms is a validated QOL instrument that assesses patient perception of overall improvement after surgical interventions for POP.12 The scale rates the patient's improvement or worsening of prolapse symptoms relative to baseline. The scale is as follows: 1- Very much better; 2- Much better; 3- A little better; 4- No change; 5- A little worse; 6- Much worse; 7- Very much worse. Assessments were performed at 6-month intervals beginning 6 months after the index procedure. | 36 months | 
| Number of Participants With Re-Intervention or Re-Surgery | Absence of re-intervention or re-surgery for recurrence or persistence of POP or Xenform exposure/erosion | 36 months | 
| Surgical Success | Surgical success based on the following composite outcome: Subjective success: Patient denied symptoms of vaginal bulging per PFDI-20 question 3, answering no or yes but Not at all bothersome (˂ 2) Anatomic success (in the operated compartment): Anterior Segment: No anterior prolapse at or beyond the hymen or POP-Q point Ba ˂ 0 Apical Segment: The vaginal apex did not descend more than one-half into the vaginal canal (i.e., POP-Q point C ˂ 1/2 TVL) for multi-compartment prolapse or POP-Q point C ˂ 0 for prolapse of the apical compartment alone No retreatment for POP (treated segment): No additional surgical treatment for POP in the segment(s) of the vagina treated at the index surgery or no pessary use since index surgery ('treated segment' refers to the target compartments in this study, which are the anterior and apical compartments) | 36 months | 
| Incidence of Complications | Incidence of the following device-related or procedure-related adverse events (AEs): pelvic pain, infection, vaginal shortening, atypical vaginal discharge, neuromuscular problems, vaginal scarring, de novo vaginal bleeding, fistula formation and/or de novo voiding dysfunction. | 36 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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POP, Transvaginal, Native Tissue Repair, Repair Augmented with Mesh, Biologic Graft, Pelvic Organ Prolapse