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| General |
| Study Status |
Delayed |
Application Number /
Requirement Number |
P100006 S005/ PAS001 |
| Date Original Protocol Accepted |
06/11/2019
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| Date Current Protocol Accepted |
06/11/2019
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| Study Name |
Long-term PAS
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| Device Name |
AUGMENT INJECTABLE
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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: At least 22 yrs
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| Detailed Study Protocol Parameters |
| Study Objectives |
The study is designed to assess the long-term (out to 6 years post-op) performance of AUGMENT Injectable compared to autograft by continued follow-up of available subjects from several prospective clinical studies (protocols BMTI-2009-01, BMTI-2010-01, and BMTI-2006-01 (autograft only)). No new subjects will be enrolled. Subjects and radiologists will remain blinded. Subjects will be informed of their treatment after the last evaluation.
Study is intended to address the following questions:
Can it be assessed and confirmed that bridging bone occurs in the long-term after AUGMENT® Injectable has been resorbed?
Are the improvements in clinical outcomes associated with the use of AUGMENT® Injectable sustained long-term?
Does the promotion of existing tumors from a nonmalignant to malignant state at longer time-points in patients treated with AUGMENT® Injectable exceed the expected rate of promotion in patients not treated with AUGMENT® Injectable or other growth factors used to promote fusion?
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| Study Population |
study group: AUGMENT Injectable graft with fused joints stabilized by metallic fixation hardware
control group: autograft with fused joints stabilized by metallic fixation hardware
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| Sample Size |
88 projected from 179 potential prior subjects
actual sample size may be modified to address discrepancies
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| Key Study Endpoints |
Primary Effectiveness Endpoints:
Pain on weight bearing (via VAS)
Confirmation of bridging bone via CT
Subject function as determined by AOFAS, FFI
Primary Safety Endpoints:
Presence of all treatment related 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
rhPDGF-BB antibody status
Significant medical conditions, including incidence of cancer
Presence of clinically important events
Functional Assessments
Subjects will assessed using the pain, function and quality of life data instruments:
Fusion Site Pain via VAS score (FSP)
Weight Bearing Pain Assessment at Fusion Site via VAS score (WBP)
Graft Harvest Site Pain via VAS score (GHSP)
Foot Pain and Disability Index (FFI)
AOFAS Hindfoot/Ankle Score (AOFAS)
Safety Assessments
Subjects will be assessed for safety parameters and events, including:
Presence of all treatment related adverse events
Presence of serious unanticipated adverse device effects (UADE)
rhPDGF-BB antibody status
Presence of clinically important events as defined below:
- Musculoskeletal and connective tissue disorders (severe pain,
swelling and/or arthralgia in the treated foot/ankle joint(s));
- Additional surgery of the original treated joint due to non-union.
- Neoplasms benign, malignant and unspecified (including cysts
and polyps) (all lower level terms associated with neoplasms)
- Complications related to bone graft harvest site
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| Follow-up Visits and Length of Follow-up |
Subjects will be followed out to at least 5 years post-op
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
One hundred and thirty-one (131), 53 AUGMENT® Injectable and 78 Autograft
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| Actual Number of Sites Enrolled |
15
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| Patient Follow-up Rate |
Follow-up Rate Follow-up rate is 139% (131/94)
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| Final Safety Findings |
Safety Results 109 adverse events (AEs) were reported in 41 subjects (31.78%), with the autograft group exhibiting a higher overall event rate (58 events in 27 subjects, 35.06%) compared to the AUGMENT® Injectable group (51 events in 14 subjects, 26.92%), and musculoskeletal/connective tissue disorders representing the largest event category.
Only 3 events in 2 AUGMENT® Injectable subjects, with a single case of Staphylococcal osteomyelitis classified as possibly device-related.
Secondary surgical interventions revealed a higher hardware removal rate in the AUGMENT® Injectable group (17.31%, 9 procedures) versus autograft (9.09%, 7 procedures), while revision rates were slightly higher in the autograft group (3.90%, 3 procedures vs. 1.92%, 1 procedure).
No unanticipated adverse device effects (UADEs) identified.
No serious or unanticipated adverse events related to AUGMENT® Injectable were reported during this reporting period.
Thirteen deaths were reported across both groups (5 AUGMENT® Injectable, 8 autograft), with no AEs classified as resulting in death during the study period.
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| Final Effect Findings |
Primary endpoint was met. Change in WBP from baseline: AUGMENT® Injectable –53.4±3.42 mm vs. autograft –55.1±2.73 mm; LS mean difference 1.7 (95% CI: –7 to 11); 1-sided 95% UCL = 9 < NI margin of 15 mm (Table 10). This demonstrates non-inferiority. Clinically significant WBP improvement (=20 mm decrease) also met non-inferiority: 1-sided 95% LCL = 0.71 > 0.50; PS-adjusted AI 88.63% vs. autograft 80.91%.
However, three binary secondary endpoints were not met (clinically significant AOFAS improvement; clinically significant FFI improvement; CT FCOJ maintenance/improvement).
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| Study Strengths & Weaknesses |
Strengths: Prospective, Randomized, Controlled, Multi-Center study.
Weaknesses:
Lack of diversity, because the majority are Caucasian (95.35%) and non-Hispanic/Latino (97.67%), limiting generalizability.
The autograft group is disproportionately composed of subjects from BMTI-2006-01 whose index surgeries occurred 14–18 years prior to evaluation, versus 8–11 years for the comparator cohort, introducing temporal heterogeneity and cohort-level confounding across age-related bone metabolism, peri-operative care standards, and competing risks that were not present in the original pivotal design. Additionally, two subjects were excluded from the PS-matched cohort due to missing covariates, yielding a final 1:1.48 AI-to-autograft ratio that, while accommodated by the PS subclassification design, further reflects the structural imbalance of the dataset.
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| Recommendations for Labeling Changes |
A labeling change is recommended to update the device labeling with the final study results to ensure that patients and providers are aware of the long-term risk of device failure.
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