Comparison of Processed Nerve Allograft and Collagen Nerve Cuffs for Peripheral Nerve Repair

Study Overview
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Brief Summary
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Processed Nerve Allograft and Collagen Nerve Cuffs will be compared to assess safety and functional outcomes for the repair of nerve injuries in the hand.

Official Title
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A Multicenter, Prospective, Randomized, Subject and Evaluator Blinded Comparative Study of Nerve Cuffs and Avance® Nerve Graft Evaluating Recovery Outcomes for the Repair of Nerve Discontinuities

Conditions
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Peripheral Nerve Discontinuities

Intervention / Treatment
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* Biological: Processed Nerve Allograft (human)
* Device: Collagen Nerve Cuff


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Peripheral Nerve Injury Exclusion Criteria: Peripheral Neuropathy Allergic to Bovine products such as Bovine Collagen Nerve Cuff

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Processed Nerve Allograft<br>Processed Nerve Allograft | Biological: Processed Nerve Allograft (human)<br> <br> |
| Active Comparator: Collagen Nerve Cuff<br> | Device: Collagen Nerve Cuff<br>* Bovine collagen based nerve cuff<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Static Two-Point Discrimination (Pre-defined Mixed Modeling Approach) | Static two-point discrimination (s2PD) is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm (best case scenario value possible) and 15mm. The failure to respond to stimulus was pre-defined as the worst case scenario value possible (16mm). Missing or incomplete assessments were imputed as the worst case scenario value possible (16mm). Missing or incomplete data was extrapolated using a pre-defined repeated measures mixed modeling approach for calculations in this analysis. This analysis was completed on the Per Protocol population, defined as subjects with at least 6 months follow-up and no major protocol violations. | Month 12 | 
| Static Two-Point Discrimination (Data As-reported) | s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm (best case scenario value possible) and 15mm. The failure to respond to stimulus was pre-defined as the worst case scenario value possible (16mm). Missing or incomplete assessments were not imputed. This analysis was completed on the Per Protocol population, defined as subjects with at least 6 months follow-up and no major protocol violations. Data used for this analysis was from 6 months post-surgical follow-up to the date of each subject's latest completed s2PD assessment, whichever came last, assessed up to 12 months. | Up to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate for Recovery of s2PD at Month 12 (Data As-Reported) | This is the percentage of subjects who achieved sensibility as defined by s2PD 2mm-15mm at Month 12. s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. The failure to respond to stimulus was pre-defined as the worst case scenario value possible (16mm). Missing or incomplete assessments were imputed as the worst case scenario value possible (16mm). This analysis was completed on the Intent-to-Treat population, defined as all subjects who were randomized. | Month 12 | 
| Percent Recovery to Pre-Injury Baseline (Contralateral Control Value) s2PD at Month 12 (Pre-defined Modeling Approach) | This is the ratio of sensibility at Month 12 relative to sensibility at baseline for which the contralateral control value at Month 12 was used, expressed as a percentage. Pre-injury baseline was defined as s2PD at Month 12 in the contralateral digit associated with the target digit. Percent recovery to Pre-Injury Baseline was defined as: change from Pre-Injury Baseline (Contralateral control value) divided by the Pre-Injury Baseline Value *100. s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. The failure to respond to stimulus was pre-defined as the worst case scenario value possible (16mm). Missing or incomplete assessments were imputed as the worst case scenario value possible (16mm). This analysis was completed on the Intent-to-Treat population, defined as all subjects who were randomized. | Month 12 | 
| Time to Recovery of s2PD (Data As-reported) | Time to recovery of s2PD was defined as the number of months from Operative day to the return of sensory function (defined as Medical Research Council sensory function score of S3+ or greater) at Month 3, Month 6, Month 9, or Month 12. s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. S4 is s2PD of 2-6mm and S3+ is s2PD of 7-15mm. Those without S3+ and absent values were considered not recovered. This is the Intent To Treat population which includes all subjects that were randomized. Any subject with a value of s2PD of absent was considered not recovered and was therefore not included in this analysis. | Assessed at Month 3, Month 6, Month 9, Month 12 (some patients were seen for their 12-month visit up to 15 calendar months post-op) | 
| Medical Research Council (MRC) Classification for Sensory Function Scores at Month 12 (Data As-reported) | MRC classification score is a functional recovery classification. For nerves with sensory targets, outcomes resulting from static two-point discrimination and Semmes-Weinstein Monofilament pressure threshold testing are used to determine the classification score. Sensibility testing for the target repair was performed by a blinded assessor using a standardized discriminator tool and Semmes-Weinstein monofilaments. Upper bound response for static two-point discrimination was 15mm. This is the Intent To Treat population which includes all subjects that were randomized and have a reported value at Month 12. Scale range: Minimum S0 = 0 (no sensibility), S1=1, S2=2, S3=3, S3+=4, maximum S4 = 5 (normative levels of sensibility). Higher values represented better outcomes. | Month 12 | 
| Change in Pain Visual Analogue Scale (VAS) Scores at Month 12 (Pre-defined Modeling Approach) | The Visual Analog Scale (VAS) For Pain is a patient reported outcomes scale whereby the patient indicated their current pain level by making a mark on a continuous horizontal 10 centimeter (100 millimeter) line. The distance from the 0 millimeter to the patient's mark corresponds to the amount of pain the subject is currently experiencing. VAS for Pain data were recorded as the number of millimeters from the left of the line to the patients mark across the range of 0-100 millimeters, with 0 millimeter representing no pain and 100 millimeters representing the worst pain imaginable. This is the Intent To Treat population which includes all subjects that were randomized. The analysis was performed using a standard statistical analysis on Month 12 data. Missing or incomplete data was extrapolated using a pre-defined repeated measures modeling approach for calculations in this analysis. | Month 12 |