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| General |
| Study Status |
Completed |
| 522 Number / Requirement Number |
PS120001 / PSS001 |
| Date Original Plan Accepted |
09/08/2013
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| Date Current Plan Accepted |
03/11/2016
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| Study Name |
POP AE and Effectiveness rates, registry
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| Device Name |
Acell matristem pelvic floor matrix
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| Root Document Number |
K041140
K141084
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
External Registry
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| Comparison Group |
Concurrent Control
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| Analysis Type |
Analytical
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| Study Population |
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
Design: This is a multicenter, non-randomized, cohort study of MatriStem Pelvic Floor Matrix for the
treatment of transvaginal repair of POP among patients with clinically documented POP and symptomatic
POP.
Primary Objectives:
For safety, to compare the proportion of subjects noting pelvic pain in the MatriStem Pelvic Floor Matrix Group to the proportion of subjects noting pelvic pain in the non-mesh repair (NTR) Group following surgical treatment for POP. The absence of pelvic pain is defined as a subject who has not had the AE of pelvic pain reported beyond 12 weeks post-operative or, the SAE of pelvic pain reported immediately postoperative and beyond.
For effectiveness, to compare the proportion of surgical success in the MatriStem Pelvic Floor Matrix Group to the proportion of surgical success in the NTR Group following surgical treatment for POP. Surgical success is a composite effectiveness outcome that includes anatomic success, subjective success, and no retreatment for POP.
Secondary Objective:
The secondary objective is to track additional safety, effectiveness, and quality of life outcome measures in subjects undergoing surgical and non-surgical (pessary use) treatment for POP. This entails the capture of comprehensive data that includes those elements required by the FDA's requirement for post- marketing surveillance of transvaginal mesh use for POP.
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| Study Population |
Qualifying consecutive adult female subjects (18 years of age and older) will be screened according to the inclusion and exclusion criteria.
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| Sample Size |
Pelvic pain and surgical success were selected to be the co-primary safety and effectiveness endpoints, respectively, of the study. Assuming that the NTR control group has a pelvic pain rate of 57% [Columbo et al. 2000] and the mesh group has a pelvic pain rate of 40% [Carey et al. 2009], a total of 126 subjects are needed in order to demonstrate non-inferiority of the mesh at an 8% non-inferiority margin at 80% power for a one-sided 0.025 significance level. Assuming that the NTR control group has a surgical success rate of 90% and the mesh group has a rate of 90%, a total of 126 subjects are needed in order to demonstrate non - inferiority of the mesh at a 15% non -inferiority margin [Barber et al. 2009] at 80% power with a one-sided 0.025 significance level. In order to meet the sample size requirements for both endpoints, a total of 126 subjects are required. After adjusting for a 22% dropout rate [Miller et al. 2011] at the three year time point, a total of 162 subjects will be enrolled in the study.
The sponsor estimates 7 to 10 Investigational Sites will be entered into the study to enroll all subjects in a 3- year total enrollment period.
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| Key Study Endpoints |
Primary Effectiveness Endpoint: Surgical success/failure at 36 months; Primary Safety Ednpoint: Rate of serious adverse event of pelvic pain (beginning immediately postoperative) and adverse event of pelvic pain (beyond 12 weeks postoperative) that is device or procedure related as determined by independent adjudication; Secondary Endpoints: 1. Composite outcome of surgical success based on an alternate anatomic criteria at 36 months; 2. Quality of Life at baseline and 6, 12, 18, 24, 36 months; 3. Cumulative rates and severity of adverse events evaluated at 6, 12, 18, 24, and 36 months following the index procedure.
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| Follow-up Visits and Length of Follow-up |
The total length of follow-up is 36 months. Follow-up visits are scheduled at 6,12, 18, 24 and 36 months
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
A total of 161 (81 NTR; 80 MatriStem PFM) subjects were enrolled in this study
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| Actual Number of Sites Enrolled |
13
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| Patient Followup Rate |
65.8% (106/161) Overall, 70.0% (56/80) MatriStem PFM and 61.7% (50/81) NTR
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| Final Safety Findings |
Primary Endpoint:
Incidence of new pelvic pain: 2.5% (2/80) MatriStem PFM, 1.2% (1/81) NTR
Secondary Endpoints:
Cumulative rates and severity of adverse events evaluated at 6, 12, 18, 24, and 36 months following the index procedure (reported in terms of adverse events; one subject can have multiple adverse events)
6 months:
MatriStem PFM – 18.6% (19/102) Mild, 29.4% (30/102) Moderate, 2.0% (2/102) Severe
NTR – 2.5% (2/81) Mild, 45.7% (37/81) Moderate, 2.5% (2/81) Severe
12 months:
MatriStem PFM – 27.5% (28/102) Mild, 34.3% (35/102) Moderate, 2.9% (3/102) Severe
NTR – 4.9% (4/81) Mild, 60.5% (49/81) Moderate, 2.5% (2/81) Severe
18 months:
MatriStem PFM – 28.4% (29/102) Mild, 38.2% (39/102) Moderate, 2.9% (3/102) Severe
NTR – 9.9% (8/81) Mild, 67.9% (55/81) Moderate, 2.5% (2/81) Severe
24 months:
MatriStem PFM – 31.4% (32/102) Mild, 47.1% (48/102) Moderate, 3.9% (4/102) Severe
NTR – 13.6% (11/81) Mild, 70.4% (57/81) Moderate, 2.5% (2/81) Severe
36 months:
MatriStem PFM – 37.3% (38/102) Mild, 58.8% (60/102) Moderate, 3.9% (4/102) Severe
NTR – 19.8% (16/81) Mild, 77.8% (63/81) Moderate, 2.5% (2/81) Severe
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| Final Effectiveness Findings |
Primary Endpoint:
Composite success at 36 months based on:
- Anatomic success (in the targeted compartment(s)) after surgical treatment of POP will be considered met if there is no vaginal or uterine descent beyond the hymen on pelvic examination with the patient performing maximal Valsalva.
- Subjective success will be considered met if the subject denies symptoms of vaginal bulging by answering "no" to PFDI-20 question 3: "Do you usually have a bulge or something falling out that you can see or feel in your vaginal area?"
- No retreatment for POP will be considered met if the subject has had no additional surgical treatment for POP in the targeted compartment(s) or use of a pessary due to prolapse of a targeted compartment(s) since the index surgery.
57.5% (46/80) MatriStem PFM, 48.1% (39/81) NTR
Secondary Endpoints:
1. Composite outcome of surgical success based on an alternate anatomic criteria (no vaginal or uterine descent at or beyond the hymen) at 36 months: 51.3% (41/80) MatriStem PFM, 39.5% (32/81) NTR
2. Quality of Life assessments at baseline and 6, 12, 18, 24, 36 months:
Pelvic Floor Distress Inventory (PFDI-20)
Baseline: 101.4 ± 55.77 (n=80) MatriStem PFM; 106.8 ± 55.48 (n=81) NTR
6 months: 34.9 ± 30.69 (n=68) MatriStem PFM; 32.2 ± 29.94 (n=54) NTR
12 months: 34.8 ± 37.65 (n=67) MatriStem PFM; 32.9 ± 34.81 (n=58) NTR
18 months: 27.0 ± 27.82 (n=61) MatriStem PFM; 32.7 ± 31.38 (n=52) NTR
24 months: 38.0 ± 36.75 (n=59) MatriStem PFM; 28.4 ± 27.11 (n=52) NTR
36 months: 26.2 ± 26.44 (n=56) MatriStem PFM; 42.4 ± 37.85 (n=50) NTR
Pelvic Floor Impact Questionnaire (PFIQ-7)
Baseline: 63.3 ± 57.88 (n=80) MatriStem PFM; 57.4 ± 55.41 (n=81) NTR
6 months: 16.6 ± 30.00 (n=68) MatriStem PFM; 13.1 ± 31.54 (n=54) NTR
12 months: 19.3 ± 38.14 (n=67) MatriStem PFM; 9.8 ± 21.98 (n=58) NTR
18 months: 11.8 ± 31.95 (n=61) MatriStem PFM; 15.3 ± 37.98 (n=52) NTR
24 months: 12.9 ± 24.41 (n=59) MatriStem PFM; 11.8 ± 25.83 (n=52) NTR
36 months: 9.2 ± 14.64 (n=56) MatriStem PFM; 13.0 ± 23.51 (n=50) NTR
Subject Global Impression of Improvement (PGII; post-operative only)
Baseline: n/a
6 months: 3.7 ± 2.00 (n=68) MatriStem PFM; 3.7 ± 1.65 (n=53) NTR
12 months: 3.8 ± 1.93 (n=67) MatriStem PFM; 4.0 ± 2.11 (n=58) NTR
18 months: 3.6 ± 1.70 (n=61) MatriStem PFM; 4.1 ± 2.11 (n=52) NTR
24 months: 3.7 ± 1.91 (n=59) MatriStem PFM; 3.8 ± 1.90 (n=52) NTR
36 months: 3.7 ± 2.07 (n=56) MatriStem PFM; 4.4 ± 2.45 (n=50) NTR
POP/Urinary Incontinence Sexual Function Questionnaire (PISQ-12)
Baseline: 14.1 ± 6.81 (n=41) MatriStem PFM; 14.3 ± 5.45 (n=40) NTR
6 months: 10.6 ± 5.19 (n=35) MatriStem PFM; 10.6 ± 4.48 (n=34) NTR
12 months: 10.0 ± 4.26 (n=34) MatriStem PFM; 11.7 ± 4.83 (n=42) NTR
18 months: 9.7 ± 4.45 (n=33) MatriStem PFM; 10.7 ± 4.06 (n=34) NTR
24 months: 10.7 ± 5.05 (n=30) MatriStem PFM; 11.1 ± 4.61 (n=36) NTR
36 months: 9.9 ± 3.99 (n=24) MatriStem PFM; 10.5 ± 4.20 (n=31) NTR
Modified TOMUS Pain Assessment
Baseline: 11.9 ± 11.85 (n=50) MatriStem PFM; 11.9 ± 8.91 (n=53) NTR
6 months: 8.1 ± 6.56 (n=29) MatriStem PFM; 8.8 ± 6.76 (n=21) NTR
12 months: 10.2 ± 6.78 (n=26) MatriStem PFM; 7.1 ± 5.43 (n=22) NTR
18 months: 8.7 ± 7.66 (n=24) MatriStem PFM; 8.7 ± 9.27 (n=19) NTR
24 months: 8.9 ± 6.69 (n=24) MatriStem PFM; 7.0 ± 6.00 (n=20) NTR
36 months: 7.3 ± 7.58 (n=19) MatriStem PFM; 7.1 ± 3.62 (n=21) NTR
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| Study Strengths and Weaknesses |
Conclusions should be made with caution due to multiple issues that limit data interpretation. These include patients lost to follow-up, the study not meeting the prespecified sample size, missing data, and lack of diversity in the subject demographics. Due to the limited sample size of this study, no statistical conclusions could be drawn regarding the study results.
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| Recommendations for Labeling Changes |
n/a
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