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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P100006 / PAS001 |
| Date Original Protocol Accepted |
03/16/2016
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| Date Current Protocol Accepted |
03/18/2016
|
| Study Name |
Extended f/u of Premarket Cohort
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| Device Name |
AUGMENT BONE GRAFT
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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 Control
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| Analysis Type |
Analytical
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
The objective of this study is to evaluate the long-term effectiveness and safety of AUGMENT® Bone Graft vs. autoglogous bone graft. This study is a continued follow-up of the pre-market cohort.
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| Study Population |
investigational graft – Augment Bone Graft
control graft – autograft bone
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| Sample Size |
A total of 169 subjects (109 investigational and 69 control) from the original population of 414 subjects (272 investigational and 142 control) have been enrolled.
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| Key Study Endpoints |
The primary effectiveness endpoints will consist of the following:
- Demonstration of bridging bone via CT
- Patient Function as determined by Pain on Weight Bearing (via VAS), AOFAS Score and Foot Function Index (FFI)
The primary safety endpoints will consist of the following:
- Presence of all adverse events (i.e., description, frequency, incidence, time to onset of first event, severity, duration, treatments administered, etc.)
- Presence of serious unanticipated adverse device effects (UADE)
- rhPDGF-BB antibody status
- At evaluation, subjects will be interviewed regarding significant medical conditions, including incidence of cancer
- Presence of clinically important events as defined below:
o Musculoskeletal and connective tissue disorders (severe pain, swelling and/or arthralgia in the treated foot/ankle joint(s));
o Additional surgery of the original treated joint due to non-union.
o Neoplasms benign, malignant and unspecified (including cysts and polyps) (all lower level terms associated with neoplasms)
o Complications related to bone graft harvest site
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| Follow-up Visits and Length of Follow-up |
The patients will have one study visit at >5 years post-op.
Frequency of Follow-up Assessments
The patients will have one study visit at >5 years post-op.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
169
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| Actual Number of Sites Enrolled |
25
|
| Patient Follow-up Rate |
100%
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| Final Safety Findings |
Subjects implanted with AUGMENT Bone Graft experienced a higher rate of “Medically Relevant Adverse Events” compared to the autograft
control group, 42.2% compared to 28.3%, respectively. No unanticipated adverse device effects (UADE) were reported for
subjects in either group.
rhPDGF-BB antibodies were found in 13.7% of the subjects treated with AUGMENT Bone Graft. None of these subjects reported detectable
levels of neutralizing antibodies.
Clinically important events:AUGMENT Bone Graft - 23 secondary surgical interventions (SSIs) in 109 cases (21.1%). This rate was double that observed in the autograft control subjects - 6 SSIs in 60 cases (10%).
o Neoplasms benign, malignant, and unspecified (including cysts and polyps) (all lower level terms associated with neoplasms) were more
than twice as common in the subjects implanted with AUGMENT Bone Graft (26.6%) compared to the autograft control group (11.7%).
o Complications related to bone graft harvest site of the autograft control subjects included a 5% rate of significant pain at more than 5
year follow up.
o The subjects implanted with AUGMENT Bone Graft reported a similar number of events characterized as “Musculoskeletal and connective
tissue disorders” (severe pain, swelling and/or arthralgia in the treated foot/ankle joint(s)) compared to the autograft control subjects (26 of
109 (23.9%) compared to 13 of 60 (21.7%), respectively).
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| Final Effect Findings |
The rate of fusion for the subjects implanted with AUGMENT Bone Graft was numerically lower, but not statistically significant (not below
the 10% non-inferiority margin) when compared to the autograft control subjects - (92.7%-92.8%) compared to (95.0%-96.6%),
respectively.
Function outcomes as determined by Pain on Weight Bearing via VAS, AOFAS Score and Foot Function Index (FFI) exhibited lower scores or
less improvement in subjects implanted with AUGMENT Bone Graft compared with to the autograft control subjects, but these differences
were not significantly different (not below the 20 point non-inferiority margin).
Significant graft site pain was still reported in 5% of autograft control subjects at timepoints out to at least 5 years post-op.
As outlined in the approval order, the intent of the PAS was to collect longer-term data in an attempt to address the following specific clinical
questions:
• Can it be assessed and confirmed that bridging bone occurs in the long-term after Augment has been resorbed?
As with the original PMA radiographic assessments, the sponsor was not able to directly confirm the presence of bridging bone. The followup radiographic evaluations did, however, allow them to demonstrate that detrimental changes to the treated joints did not occur, i.e.,
subjects reporting initial healing did not progress to non-unions. This observation can be used to satisfy the first clinical objective of the PAS.
In order to definitively address graft resorption and fusion mass formation as evidenced by radiographically-visible bridging bone, it would have been necessary for the sponsor to perform the types of radiographic assessments requested in PAS #2, which based on agreement with FDA, was ultimately not performed.
• Are the improvements in clinical outcomes associated with the use of Augment sustained long-term?
The PAS has demonstrated that the early clinical observations, e.g., VAS pain and the various function assessments, were maintained over
the longer-term follow-up period. As a result, the second clinical objective has been satisfied.
• Does the promotion of existing tumors from a nonmalignant to malignant state at longer time-points in patients treated with Augment
exceed the expected rate of promotion in patients not treated with Augment or other growth factors used to promote fusion?
The minimal amount of data related to tumors does not support a difference in behavior between subjects receiving AUGMENT Bone
Graft compared to subjects receiving autograft bone. As part of the continued annual reporting requirements, the sponsor will continue to
report on incidences of tumors. The third clinical objective has been satisfied.
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| Study Strengths & Weaknesses |
Strength: 100% follow-up rate, there is a comparator group.
Weaknesses: Small sample size (169), lack of representativeness, e.g., 94% of subjects were White.
Labeling Change Recommended:
The PAS study design, methods and results must be included in the labeling.
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| Recommendations for Labeling Changes |
Yes
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