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| General |
| Study Status |
Completed |
| 522 Number / Requirement Number |
PS130044 / PSS001 |
| Date Original Plan Accepted |
09/10/2013
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| Date Current Plan Accepted |
04/06/2018
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| Study Name |
POP AE and Effectiveness rates, registry
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| Device Name |
Pinnacle LITE Pelvic Floor Repair Kits - Uphold Lite Posterior and Uphold
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| Root Document Number |
K122459
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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 |
Non-randomized, parallel cohort, multi-center study using PFD Registry.
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| Study Population |
This study will enroll adult (= 18), non-pregnant women who have been diagnosed with anterior and/or apical pelvic organprolapse and will undergo repair surgery, and who mayor may not also undergo a concomitant procedure (such as an anterior repair, posterior repair, hysterectomy, or sling placement for stress urinary incontinence).
If a concomitant procedure were to occur, the sling placement should be a synthetic material, however the concomitant anterior or posterior repair cannot include a mesh implant. An anterior colporrhaphy maybe performed for cystocele repair, if clinically necessary.
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| Sample Size |
Approximately 414 subjects (207 subjects per arm) from up to 40 study centers in the United States will be enrolled. Eligible number of control subjects meeting the study inclusion/exclusion criteria may be shared from the PFD Registry.
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| Key Study Endpoints |
Enrollment: Subjects will be considered enrolled in the study once an incision is made in the vaginal wall. All enrolled subjects will have been consented and assigned to receive either the treatment or control procedure per site assignment. All enrolled subjects with a surgery initiated (i.e. incision in vagina) will be considered part of the Intent-to-Treat (ITT) population for the final study analysis. All eligible ITT subjects enrolled who undergo the assigned study procedure and had no major protocol deviations will be considered part of the Per Protocol analysis.
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| Follow-up Visits and Length of Follow-up |
The length of follow-up is 3 years. Data will be collected following the procedure at 6, 12, 18, 24, and 36 months.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
There were 289 subjects enrolled from sites, 225 in the Uphold LITE arm and 64 in the native tissue repair (NTR) arm. An additional 421 NTR subjects were pulled from the AUGS PFD Registry) for a total of 710 subjects.
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| Actual Number of Sites Enrolled |
27
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| Patient Followup Rate |
12-month: 91.1% (647/710) Overall, 90.2% (203/225) Uphold LITE, 91.5% (444/485) NTR
24-month: 84.4% (599/710) Overall, 80.9% (182/225) Uphold LITE, 86.0% (417/485) NTR
36-month: 80.6% (572/710) Overall, 76.0% (171/225) Uphold LITE, 82.7% (401/485) NTR
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| Final Safety Findings |
Primary Endpoint
The following rates of severe adverse events (SAEs) were reported in the intent-to-treat (ITT) population within 36 months post index procedure using the multiple imputation method for missing data:
Uphold LITE: 3.1% (7/225) NTR: 2.7% (13/485)
Non-inferiority of Uphold LITE transvaginal mesh vs. NTR for safety was established. The use of Uphold LITE for the treatment of anterior and/or apical vaginal prolapse was as safe as NTR with respect to the overall rate of SAEs at 36 months. Please note that while the two groups had a comparable overall rate of SAEs, the types of SAEs differed between groups.
Secondary Endpoints
1. Incidence of mesh erosion, defined as the passage or perforation of mesh into hollow visceral organs, such as the bladder or rectum, per the protocol.
No reports of mesh erosion.
2. Incidence of mesh exposure, defined as mesh visualized through the vaginal epithelium, such as through a separated incision line, per the protocol.
Mesh exposure incidence within 36 months is noted at 4.9% (11/225).
3. Incidence of de novo dyspareunia
Uphold LITE: 0.9% (2/225) per 3 years NTR: 1.2% (6/485) per 3 years
4. Device or procedure related incidence of the following: pelvic pain, infection, vaginal shortening, atypical vaginal discharge, neuromuscular problems, vaginal scarring, de novo vaginal bleeding, fistula formation and/or de novo voiding dysfunction
Within 36 months post-procedure
Pelvic pain: 4.9% (11/225) Uphold LITE; 5.8% (28/485) NTR
Infection: 10.2% (23/225) Uphold LITE; 14.0% (68/485) NTR Vaginal shortening: 0.4% (1/225) Uphold LITE; 0.0% (0/485) NTR
Atypical vaginal discharge: 0.9% (2/225) Uphold LITE; 0.6% (3/485) NTR Neuromuscular problems: 4.4% (10/225) Uphold LITE; 2.9% (14/485) NTR Vaginal scarring: 0.0% (0/225) Uphold LITE; 0.2% (1/485) NTR
De novo vaginal bleeding: 0.0% (0/225) Uphold LITE; 1.4% (7/485) NTR Fistula formation: none
De novo voiding dysfunction: 7.6% (17/225) Uphold LITE; 4.7% (23/485) NTR
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| Final Effectiveness Findings |
Primary Endpoint
The following success rates were reported in the intent-to-treat (ITT) population at the 36-month follow-up time point using the multiple imputation method for missing data:
Uphold LITE: 89.2% (201/225) NTR: 80.2% (389/485)
Superiority of Uphold LITE compared to NTR could not be established. The use of Uphold LITE for the treatment of anterior and/or apical vaginal prolapse, as defined per the protocol, was comparable to NTR.
Secondary Endpoints
1. Improvement in subject specific outcomes at 36 months compared to Baseline (pelvic floor symptoms (PFDI-20), QOL (PFIQ-7), change in sexual functioning (PISQ- 12), TOMUS pain scale)
PFDI-20: -73.5 ± 59.4 (170 subjects) Uphold LITE; -77.2 ± 56.1 (400 subjects) NTR
PFIQ-7: -48.1 ± 62.9 (167 subjects) Uphold LITE; -41.9 ± 55.0 (399 subjects) NTR
PISQ-12: 4.2 ± 5.8 (55 subjects) Uphold LITE; 4.3 ± 5.8 (156 subjects) NTR
TOMUS: -4.3 ± 8.7 (170 subjects) Uphold LITE; -4.0 ± 8.3 (399 subject) NTR
2. Assessment of subject’s level of improvement, measured by the Patient Global Impression of Improvement for Prolapse (PGI-I for Prolapse)
Uphold LITE: 1.6 ± 1.0 (170 subjects)
NTR: 1.4 ± 0.9 (399 subjects)
3. Absence of re-intervention or re-surgery for recurrence or persistence of POP or Uphold LITE exposure/erosion
Recurrence or persistence of POP: 2.7% (6/225) Uphold LITE; 3.5% (17/485) NTR
Mesh exposure: 72.7% (8/11) of exposure events required intervention
4. Surgical success
Uphold LITE: 83.5% (188/225) NTR: 72.7% (353/485)
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| Study Strengths and Weaknesses |
I. There is an unbalanced rate of subjects lost to follow-up between the Uphold LITE treatment arm and the NTR control arm beginning with 18-month follow-up and carried through to 36 months. The unbalance of the missing data should not be considered missing at random. The estimated treatment effect could be biased no matter which statistical analysis method is used.
II. Qualitative interaction effect of treatment by propensity score stratum is observed in terms of primary effectiveness endpoint at 36-month, i.e., the observed treatment differences between treatment arms are not in the same direction across different propensity score stratums. Caution should be exercised when interpreting the overall data, especially with respect to whether the study conclusion based on the pooled data is applicable to certain stratums or certain subpopulations.
III. The adverse event (AE) rates presented in the current clinical report could underestimate the actual AE rates since for those subjects who discontinued or were lost to follow-up prior to 36 months, they were imputed as no events if they had not reported any AEs prior to discontinuation.
IV. There are some limitations to the interpretation of this study due to multiple issues like patients lost to follow up, missing data, the lack of diversity in the subject’s demographics, the imbalance of baseline characteristics in each arm, how each investigator reports adverse events and the distinction between surgical procedures done in the office or in the hospital to assess whether they should be named a surgical procedure or office-based.
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