Comparison of Processed Nerve Allograft and Collagen Nerve Cuffs for Peripheral Nerve Repair (RECON)

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

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Nerve Discontinuities
• Intervention / Treatment: Biological: Processed Nerve Allograft (human); Device: Collagen Nerve Cuff

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University California, Davis
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Miami, Florida, United States, 33146
      • University of Miami
    • Tampa, Florida, United States, 33609
      • Florida Orthopaedic Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hand to Shoulder Center
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University Of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Curtis National Hand Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin Healthcare
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Hand Surgery Specialists of Nevada
  • New York
    • Rochester, New York, United States, 14627
      • University of Rochester Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 16801
      • Penn State Universtiy
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Rothman Institute
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Univeristy of Virginia
    • Richmond, Virginia, United States, 23228
      • Virginia Commonwealth University Medical Center
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Marshall Orthopaedics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Peripheral Nerve Injury

Exclusion Criteria:

• Peripheral Neuropathy
• Allergic to Bovine products such as Bovine Collagen Nerve Cuff

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Processed Nerve Allograft	Biological: Processed Nerve Allograft (human)
Active Comparator: Collagen Nerve Cuff	Device: Collagen Nerve Cuff; Bovine collagen based nerve cuff

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Persistent and Unresolved Pain (Data As-reported)	No interpolated data or modeling was used for this analysis. This analysis was completed for Adverse Event (AE) criteria related to pain and hypersensitivity (Pain, Pain in Extremity, Hypersensitivity, Hypersensitivity at implant site, Neuroma, and derivations of these descriptors) beginning after Operative Day (Operative Day+1). Revision surgeries for Pain-Related conditions documented as Ongoing were also included. Recovered/Resolved AEs were not included in the analysis unless the resolution was surgical revision. Unrelated AEs were also not included in this analysis. This is the Safety population which includes all subjects that received a nerve repair.	Operative Day+1, Month 1, Month 3, Month 6, Month 9, Month 12

Collaborators and Investigators

• Sponsor: Axogen Corporation
• Investigators: Principal Investigator: Jonathan E Isaacs, MD, Virginia Commonwealth University Medical Center; Principal Investigator: L. Scott Levin, MD FACS, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: March 4, 2013
• First Submitted That Met QC Criteria: March 8, 2013
• First Posted (Estimated): March 12, 2013

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: ANG-CP-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No