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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P060037 / PAS001 |
| Date Original Protocol Accepted |
11/06/2008
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| Date Current Protocol Accepted |
11/16/2016
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| Study Name |
Long Term Study
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| Device Name |
NEXGEN LPS-FLEX MOBILE AND LPS-MOBILE BEARING KNEE SYSTEM
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Concurrent & Historical 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 |
Objective: to assess the long-term safety and effectiveness of the NexGen® LPS-Flex Mobile Bearing Knee in the treatment of patients with severe knee pain or degenerative knee disease, in comparison with the LPS-Flex Fixed Bearing Knee.
Design: a prospective, multi-center, parallel group, controlled post-approval study comparing the clinical performance of the LPS-Flex Mobile Bearing Knee with the LPS-Flex Fixed Bearing Knee. The study includes both continued follow-up of premarket IDE cohorts through the 10th post-operative year and new enrollment and follow-up of patients through their 5th post- operative year.
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| Study Population |
Study population is as per device indication. This device is indicated for patients with severe knee pain and disability due to: - Rheumatoid arthritis (RA), osteoarthritis (OA), primary and secondary traumatic arthritis, polyarthritis. - Collagen disorders, and/or avascular necrosis of the femoral condyle or pseudo-gout - Post-traumatic loss of joint configuration, particularly when there is patellofemoral erosion, dysfunction or prior patellectomy.- Moderate valgus, varus, or flexion deformities. Group 1 consists of patients who received either the LPS-Flex Fixed Bearing Knee
or the LPS-Flex Mobile Bearing Knee during the active IDE, completed the IDE study and have given written consent to participate in the post-approval study. Group 2 patients will be enrolled into a single-arm, historically controlled, mid-term study (5 years) and this group will consist of 100 patients who undergo Total Knee Replacement with the LPS-Flex Mobile Bearing Knee after the device approval.
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| Sample Size |
The sample size is 400 patients. Group 1 approximately 300 patients already implanted during the IDE study with either the LPS-Flex Fixed Bearing Knee (control population, N=150) or the LPS-Flex Mobile Bearing Knee device (N=150) at one of approximately 10 sites. Group 2 100 patients who are eligible for a total knee replacement, have chosen to receive the LPS-Flex Mobile Bearing Knee, and meet the PAS eligibility criteria.
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| Key Study Endpoints |
A composite clinical success, defined by the following criteria, will be used as the primary outcome: - Knee Society assessment score greater than/equal to 70 points- Knee Society function score greater than/equal to 70 points - No intended, actual, or planned removal of any component of the knee system - Absence of severe knee-related complications - An absence of subsidence of greater than or equal to 2 millimeters and an absence of both osteolysis and radiolucencies greater than or equal to 2 millimeters as determined by independent radiographic reviewer. Safety endpoints: revision, removal and device-related adverse Secondary endpoint: Quality of Life
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| Follow-up Visits and Length of Follow-up |
Group 1: 10 years post-operation
Group 2: 5 years post-operation
Group 1: Postoperatively at 4 years (if applicable), 5 years (if applicable), 6 years, 8 years and 10 years.
Group 2: Postoperatively at 6 weeks, 6 months, and at 1, 2, 3, 4 and 5 years post-operation.
The patients will be followed at 6 weeks, 6 months and at annual increments up to 5 years post-operation for Group 2/And followed at 5, 6, 8/And 10 years post-operation for Group 1.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
A subset of 146 subjs were enrolled into group 1 from the original IDE study for continued f/u to 10 yrs. Of these 146 subjs, 69 subjs received LPS-Flex Mobile-Bearing Knees which includes 66 unilateral knees and 3 bilateral knees in the investigational arm. A total of 77 subjs received unilateral LPS-Flex Fixed- Bearing Knees and were enrolled into the control arm.
Based on the sponsor’s analysis of the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), 7,686 subjs received NexGen LPS-Flex Mobile tibial knees and 427,770 subjs received other tibial knees.
Group 2: 133 subjs were enrolled. Of these, 120 pts received LPS-Flex Mobile-Bearing Knees (106 subjs received unilateral knees and 14 subjs received bilateral knees), and 13 subjs received other implants and were later terminated.
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| Actual Number of Sites Enrolled |
Group 1: 10
Group 2: 3
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| Patient Follow-up Rate |
Group 1:
Complete Data: 61.5% (40/65) of subjs w/mobile-bearing knees and 68.0% (51/75) of subjs w/fixed- bearing knees had Complete Data at 10 yrs.
Any Data: 64.6% (42/65) of subjs w/mobile-bearing knees and 73.3% (55/75) of subjs w/fixed-bearing knees had Any Data at 10 yrs.
Group 2:
Complete Data: 67.0% (71/106) of subjs had Complete Data at 5 yrs.
Any Data: 69.8% (74/106) of subjs had Any Data at 5 yrs.
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| Final Safety Findings |
Group 1
Device Revision Rates
For PAS Group 1 at 10 yrs, there were 2.9% (2/69) revisions in mobile-bearing knees compared to 1.3% (1/77) in fixed-bearing knees. The sponsor analyzed the AOANJRR and found that at 10 yrs, there were 4.3% [95% CI (Confidence Interval): 3.7%, 4.9%] revisions in mobile tibial knees compared to 5.5% (95% CI: 5.4%, 5.6%) in other tibial knees. Additional analysis showed that subjects receiving NexGen LPS-Flex Mobile tibial knees showed survivorship of 98.7% (95% CI: 98.3%, 99.0%) at 2 yrs, 97.5% (95% CI: 96.9%, 97.9%) at 5 yrs, and 96.2% (95% CI: 95.4%, 96.8%) at 10 yrs.
Device Removals
At 10 yrs, 4.3% (3/69) of mobile-bearing knees and 1.3% (1/77) of fixed-bearing knees in IDE group 1 subjs had device removal.
Adverse Events
At 10 yrs, 56.5% (39/69) of subjs w/mobile-bearing knees reported an adverse event compared to 64.9% (50/77) of subjs w/fixed-bearing knees. Among those events, 4.4% (4/90) of adverse events were device-related for mobile-bearing knees and 0% (0/126) were device-related for fixed-bearing knees. At 10 yrs, 4.3% (3/69) of subjs w/mobile-bearing knees experienced severe knee-related complications compared to 2.6% (2/77) of subjs w/fixed-bearing knees.
Group 2
Device Revisions
Overall, there were 5.8% (7/120) revisions and 1.7% (2/120) re-revisions in PAS Group 2 patients who received mobile-bearing knees at 5 years, compared to 2.9% (2/69) revisions in mobile-bearing knees and 1.3% (1/77) revisions observed in fixed-bearing knees from IDE Group 1 patients at 10 years.
Device Removals
There were 5.0% (6/120) device removals/ reoperations in PAS group 2 patients at 5 years compared to 4.3% (3/69) in subjects with mobile- bearing knees and 1.3% (1/77) in subjects with fixed-bearing knees in IDE group 1 at 10 years.
Adverse Events
In PAS Group 2, 72.5% (87/120) of subjects with mobile-bearing knees reported an adverse event compared to 56.5% (39/69) of PAS Group 1 subjects with mobile-bearing knees and 64.9% (50/77) of PAS Group 1 subjects with fixed-bearing knees at 5 years. There was no device- related adverse events reported at 5 years for PAS Group 2 patients compared to 4.4% (4/90) in PAS Group 1 subjects with mobile-bearing knees and 0% (0/126) of PAS Group 1 subjects with fixed-bearing knees at 10 years.
In PAS Group 2, 9.2% (11/120) of subjects with mobile-bearing knees experienced severe knee -related complications at 5 years compared to 4.3% (3/69) of PAS Group 1 subjects with mobile-bearing knees and 2.6% (2/77) of PAS Group 1 subjects with fixed-bearing knees at 10 years.
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| Final Effect Findings |
Composite Clinical Success
Data was not available for composite clinical success at 10 years because of increased rates of loss to follow-up in the long-term IDE cohort. The composite clinical success was also not available from the AOANJRR.
Knee Society Score Assessment (KSSA) Clinical Outcome
At 10 years, 92.1% (35/38) of Group 1 subjects with mobile-bearing knees and 95.9% (47/49) of subjects with fixed-bearing knees were above 70 points for the KSSA outcome.
Knee Society Score Function (KSSF) Clinical Outcome
At 10 years, 76.9% (30/39) of Group 1 subjects with mobile-bearing knees and 70.0% (35/50) of subjects with fixed-bearing knees were above 70 points for the KSSF outcome.
Radiographic Clinical Outcome (Osteolysis and Radiolucency)
At 10 years, radiographically, 9.1% (7/77) of Group 1 subjects with fixed-bearing knees and 1.4% (1/69) of subjects with mobile-bearing knees had significant radiolucencies greater than or equal to 2 mm.
Quality of Life Evaluation (SF-12)
Mental Health: SF-12 Mental Health Score for Group 1 subjects with fixed-bearing knees improved slightly from 4 years (50.5%) to 10 years (54.2%). Subjects with mobile-bearing knees improved as well from 55.4% at 4 years to 56.5% at 10 years.
Physical Health: SF-12 Physical Health scores for Group 1 subjects with fixed-bearing knees changed slightly from 4 years (45.7%) to 10 years (45.2%). For subjects with mobile-bearing knees at 4 years the score was 52.1% and at 10 years 48.6%.
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| Study Strengths & Weaknesses |
Strengths: The Group 1 PAS is a long-term f/u up of a subset of IDE study subjs for 10 yrs post-surgery. An analysis performed by the sponsor revealed a large sample of pts in real-world setting (n=7,686) from the AOANJRR that was used to supplement existing data. The sponsor was able to extrapolate safety and effectiveness from the registry data by comparing variables such as reasons for revision, sex distribution and primary diagnosis between the subjects in the registry and PAS Group 1.
Weaknesses: The study failed to meet the enrollment target of 300 subjs. Only 61.5% (40/65) of subjs w/mobile-bearing knees had complete data at 10 yrs. The missing data may lead to a potential for selection bias. The sponsor was not able to provide a composite clinical success at 10 yrs because of high rates of loss to f/u in the long-term cohort. A one-to-one comparison of registry data to PAS study results could not be performed due to limited demographic data (e.g., primary diagnosis, gender, and reason for revision). Data from AOANJRR were only presented for revision rates and the sponsor was not able to report other study endpoints such as composite clinical success, data on pain, function, range of motion, deformity, radiographic parameters, health status, and detailed information on adverse events. Therefore, data collected from the registry was not adequate to supplement the original PAS.
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| Recommendations for Labeling Changes |
It is recommended that the labeling be updated to reflect the final study results. A final labeling supplement was submitted and approved.
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