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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P080013 / PAS001 |
| Date Original Protocol Accepted |
09/04/2009
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| Date Current Protocol Accepted |
02/03/2016
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| Study Name |
DuraSeal Exact Spine Sealant System
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| Device Name |
DURASEAL EXACT SPINE SEALANT SYSTEM
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| General Study Protocol Parameters |
| Study Design |
Prospective & Retrospective 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: Estimate the rates of post-operative CSF leak, deep surgical site infection and neurological SAEs within 90 days for DuraSeal Exact Spine Sealant and to compare these rates to the corresponding rates for Control. Design: a multi-center, non-randomized, Post Approval study with a prospective treatment arm and a retrospective control arm.
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| Study Population |
For the retrospective controls (standard of care), subjects with fewer than 45 days of follow-up will be considered incomplete.
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| Sample Size |
The DuraSeal Exact Spine Sealant prospective treatment arm will enroll up to 489 subjects in order to obtain a total of 402 evaluable subjects with 90 day follow-up data.
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| Key Study Endpoints |
The primary endpoint is the occurrence of post-operative CSF leaks within 90 days after the spine surgical procedure.
A CSF leak is defined as a CSF fistula or a pseudomeningocele* confirmed by clinical examination or diagnostic testing (i.e., MRI or CT) whether or not treatment such as surgical repair or drainage is required.
* Pseudomeningocele noted on a diagnostic test must be confirmed by the study investigator
Secondary endpoints are the occurrence of the following events (within 90 days following the surgical procedure):
Deep Surgical Site Infections (DSSI) as defined per the CDC guidelines
All neurological SAEs
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| Follow-up Visits and Length of Follow-up |
For retrospective controls (standard of care), a patient will be considered completed if there is follow-up of at least 45 days.
New study sites that do not have 90 day standard of care visits will enroll prospective subjects only (DuraSeal and/or Control). This would allow new sites to contribute subjects prospectively inside the study window (60 to 120 days), and allow control over follow-up compliance.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
489 (treatment group) + 435 (control arm)
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| Actual Number of Sites Enrolled |
36
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| Patient Follow-up Rate |
(429+406) / (489+435) * 100% = 90.4%
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| Final Safety Findings |
Primary Endpoint: CSF Leakage
DuraSeal Sealant was non-inferior compared with the control device in CSF Leakage in this study.
Of the 886 study subjects on whom data were available, 58 (6.6%) subjects (DuraSeal Exact Spine Sealant: 30 [6.6%]; Control arm: 28 [6.5%]) experienced a CSF leak within 90 days after the spine surgical procedure. The difference estimate and its 95% CI (%) between treatment arms was reported as -0.9 (- 3.7, 2.0) from an unstratified analysis and as -0.5 (-3.4, 2.3) from a stratified analysis by propensity score quintile,
Surgical Site Infections (SSI):
There was no statistically significant difference in distribution of subjects with deep Surgical Site Infection (SSI) between the treatment groups
As per CDC guideline, SSIs have been categorized into superficial SSI, DSSI, and organ/space SSI. There was a statistically significant higher proportion of subjects with superficial SSIs in the DuraSeal Exact Spine Sealant arm compared to the Control arm (2.8% versus 0.5%; p = 0.0076). Although the proportion of subjects with DSSI (2.1% versus 1.6%) and organ space SSIs (0.2% versus 0%) was numerically higher in the Control arm against the DuraSeal Exact Spine Sealant arm, the difference was not statistically significant.
Adverse Events (AEs)
There was no statistically significant difference in the proportion of subjects with any AE between the DuraSeal Exact Spine Sealant and the Control arms
Ninety-two (92) subjects experienced at least one AE (DuraSeal Exact Spine Sealant arm: 51
[10.4%] subjects; Control arm: 41 [9.4%] subjects). There was no statistically significant difference in the proportion of subjects with at least one AE between the DuraSeal Exact Spine Sealant and the Control arms (p=0.6109).
There was no statistically significant difference in the proportion of subjects with any SAE between the DuraSeal Exact Spine Sealant and the Control arms
There were 75 serious AEs reported during the study (DuraSeal Exact Spine Sealant arm: 42 [8.6%] subjects; Control arm: 33 [7.6%] subjects). There was no statistically significant difference in the proportion of subjects with at least one SAE between the DuraSeal Exact Spine Sealant and the Control arms (8.6% versus 7.6%; p=0.5755). No UADEs were reported during this study.
There was no statistically significant difference in the proportion of subjects between the treatment groups in terms of AE relatedness to the study device (p = 0.5370) and AE severity (p= 0.5979).
By relatedness, the AEs were related to the device in 22 subjects (DuraSeal Exact Spine Sealant arm: 18 subjects; Control arm: 4 subjects); There was no statistically significant difference in the proportion of subjects with definite, probable, possible, or unknown relationship/impossible to determine relatedness to the study device for AEs between the two treatments.
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| Final Effect Findings |
There was no effective endpoints, the primary and secondary endpoints are all safety related.
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| Study Strengths & Weaknesses |
Strength
Multi-center prospective treatment group with relatively large sample size so that the study is sufficiently powered and the sample is representative to the general population; Using a large number of patient with standard of care as the control arm; A pre-specified statistical plan in place to test the non-inferiority margin of 5% was in place before the study initiation.
Weakness
This is not a randomized study. The treatment group was compared with a retrospectively selected historical cohort with the standard of care. As a result, the two groups may be selected from two populations that are not exactly the same, and this may impact the result of the study.
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| Recommendations for Labeling Changes |
It is recommended that the sponsor change the conclusion regarding the risk of Surgical Site Infection to accurately reflect the PAS results.
Original language: ‘there was no statistically significant difference in distribution of subjects with any Surgical Site Infection (SSI) between the treatment groups (p=0.2295)’ New language: ‘there was no statistically significant difference in distribution of subjects with deep
Surgical Site Infection (SSI) between the treatment groups’.
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