Uphold LITE Post-Market Surveillance Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare transvaginal mesh repair to traditional native tissue repair in women surgically treated for anterior and/or apical pelvic organ prolapse.

Detailed Description
-----------------
The primary objective is to evaluate clinical effectiveness of transvaginal repair with mesh (Uphold LITE) against traditional native tissue repair in women surgically treated for anterior and/or apical pelvic organ prolapse. Secondary objectives are to evaluate Uphold LITE-related complications and subject reported outcomes. The primary endpoint of the study is to achieve superiority of transvaginal repair with mesh (Uphold LITE) 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 mesh (Uphold LITE) 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
-----------------
A Prospective, Non-Randomized, Parallel Cohort, Multi-center Study of Uphold LITE Versus Native Tissue for the Treatment of Women With Anterior/Apical Pelvic Organ Prolapse

Conditions
-----------------
Pelvic Organ Prolapse

Intervention / Treatment
-----------------
* Device: Uphold Lightweight Vaginal Support System
* Procedure: Traditional native tissue repair


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is female Subject is ≥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 or (for prolapse of the anterior compartment alone) 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 of 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 must be willing to provide written informed consent Subject is willing and able to comply with the follow-up regimen Exclusion Criteria: 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), Marfans syndrome, Ehlers Danlos, collagenosis, polymyositis polymyalgia rheumatica) 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 has a previous prolapse repair with mesh in the target compartment Subject is planning to undergo a concomitant repair with use of mesh in the non-target compartment Subject is not able to conform to the modified dorsal lithotomy position Subject has chronic systemic pain that includes the pelvic area or chronic focal pain that includes the pelvis Subject has uncontrolled diabetes mellitus (DM) Subject is currently participating in or plans to participate in another device or drug study during this study Subject has a known hypersensitivity to polypropylene mesh Subject is pregnant or intends to become pregnant during the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Uphold Lightweight Vaginal Support System<br>Transvaginal repair with mesh (Uphold LITE) | Device: Uphold Lightweight Vaginal Support System<br>* Pelvic organ prolapse repair via transvaginal mesh (Uphold LITE)<br>* Other names: Uphold LITE;|
| Active Comparator: Traditional native tissue repair<br>Sacrospinous ligament fixation or uterosacral ligament suspension and/or colporrhaphy | Procedure: Traditional native tissue repair<br>* Sarcrospinous ligament fixation or uterosacral ligament suspension and/or colporrhaphy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint - Number of Participants With Composite Anatomic and Symptomatic Success at 36 Months | Success based on a composite of objective and subjective measures: Objective success was achieved by the subject having an anatomic outcome defined as the leading edge of prolapse at or above the hymen in the operated compartment: Anterior segment: Leading edge of anterior prolapse was at or above 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 single compartment apical prolapse. 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). 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 since index surgery (i.e., 'treated segment' refers to the target compartment). | 36 Months | 
| Co-Primary Safety Endpoint - Number of Participants With One or More Serious Device-Related and/or Procedure-Related Complications at 36 Months | A co-primary endpoint of the study was to achieve non-inferiority of transvaginal repair with Uphold LITE vs. NTR for safety by comparing the overall complication rate (device-related and/or procedure-related SAEs) at 36 months | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint - Number of Participants With Mesh Erosion and Exposures Over Time in Intent-to-Treat Subjects | Provides a summary of the number of subjects who reported mesh erosion or exposure at each of the study follow-up time points. | 6 Month, 12 Months, 18 Months, 24 Months, 36 Months, Overall | 
| Secondary Endpoint - Number of Participants With One or More Device-Related and/or Procedure-Related Adverse Events | Number of subjects with the following device-related and/or procedure-related adverse events: de novo dyspareunia, pelvic pain, infection, vaginal shortening, atypical vaginal discharge, neuromuscular problems, vaginal scarring, de novo vaginal bleeding, fistula formation, and/or de novo voiding dysfunction. The Intent-to-Treat (ITT) population includes all enrolled subjects who had a surgery initiated; the As Treated population includes all subjects who successfully completed the surgical procedure. Both ITT and As Treated populations are identical to the Overall Number of Participants Analyzed. | 36 Months | 
| Secondary Endpoint - PFDI-20 Change From Baseline in Intent-to-Treat Subjects | The Pelvic Floor Distress Inventory-20 (PFDI-20) consists of three components: Pelvic Organ Prolapse Distress Inventory (POPDI; 6 questions), Urinary Distress Inventory (UDI; 6 questions), and Colorectal-Anal Distress Inventory (CRADI; 8 questions). 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). Reported outcomes are the change from Baseline for the time periods indicated. | 6 Month, 12 Months, 18 Months, 24 Months, 36 Months | 
| Secondary Endpoint - PFIQ-7 Change From Baseline in Intent-to-Treat Subjects | The Pelvic Floor Impact Questionnaire (PFIQ-7) is composed of 3 separate but related assessments: the Urinary Impact Questionnaire, addresses the impact of urinary incontinence symptoms, the Colorectal-Anal Impact Questionnaire addresses the impact of colorectal-anal or bowel symptoms, and the Pelvic Organ Prolapse Impact Questionnaire 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, which ranges from 0-300. A lower score means there is a lesser effect on quality of life. | 6 Month, 12 Months, 18 Months, 24 Months, 36 Months | 
| Secondary Endpoint - PISQ-12 Change From Baseline in Intent-to-Treat Subjects | The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) is a validated short form that can be used to ascertain improvement in sexual function and desire in women undergoing therapy for pelvic organ prolapse. The PISQ-12 consists of 12 questions graded on a five-point Likert scale ranging from 0 (always) to 4 (never). Values range from 0-48 and a higher score indicates better sexual function. Reported outcomes are the change from Baseline for the time periods indicated. | 6 Month, 12 Months, 18 Months, 24 Months, 36 Months | 
| Secondary Endpoint - TOMUS Pain Score Change From Baseline in Intent-to-Treat Subjects | 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. There are seven (7) questions each with a maximum score of 10 and a possible score range of 0-70. Reported outcomes are the change from Baseline for the time periods indicated. | 6 Month, 12 Months, 18 Months, 24 Months, 36 Months | 
| Secondary Endpoint: PGI-I for Prolapse Symptoms in Intent-to-Treat Subjects | 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 pelvic organ prolapse. 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. | 6 Month, 12 Months, 18 Months, 24 Months, 36 Months | 
| Secondary Endpoint - Number of Participants With Intervention for Recurrent Prolapse and Complications at 36 Months Post Index Procedure | Compares the office-based and surgical intervention for recurrent prolapse and complications between the Uphold LITE arm and the NTR arm 36 months from the index procedure in the Intent-to-Treat (ITT) and As Treated populations. The ITT population includes all enrolled subjects who had a surgery initiated; the As Treated population includes all subjects who successfully completed the surgical procedure. Both ITT and As Treated populations are identical to the Overall Number of Participants Analyzed. | 36 Months | 
| Secondary Efficacy Endpoint - Number of Participants With Composite Anatomic and Symptomatic Success at 36 Months | Secondary efficacy endpoint defined similarly to the primary efficacy endpoint except for the definition of objective success. Objective success for this endpoint is defined as: Anatomic success in the operated compartment was achieved by: 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 single compartment apical prolapse. Subjective success was achieved if the patient denied symptoms of vaginal bulging per PFDI-20 question 3, answering no or yes but Not at all bothersome (< 2). No retreatment for POP: No additional surgical treatment for POP in 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 | 

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